Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title
Toward Translation of Nanotechnology Cancer Interventions (TTNCI; R01 Clinical Trial Not Allowed)
Activity Code

R01 Research Project Grant

Announcement Type
Reissue of PAR-22-071
Related Notices
  • April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Funding Opportunity Number (FON)
PAR-25-336
Companion Funding Opportunity
None
Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)
93.395
Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO), entitled "Toward Translation of Cancer Nanotechnology Interventions (TTNCI)" is designed to enable the translation of nanotechnology-based cancer interventions relying on nanoparticle formulations and/or nano-devices. Through the TTNCI initiative, the National Cancer Institute (NCI) encourages applications for advanced pre-clinical research, supporting translation of nanotechnology-based cancer diagnostics and therapeutics. TTNCI awards are expected to mature experimental nanomedicines designed for highly relevant cancer clinical objectives with a strong potential to improve cancer treatment effectiveness. It is expected that improvement of treatment effectiveness will occur due to the combination of nanoparticle/nano-device structural design and/or therapeutic/diagnostic cargo which is delivered. TTNCI awards are expected to enable further development of proposed nanotechnology-based interventions to the stage in which they could continue on a developmental path towards the NCI Experimental Therapeutics (NExT) and other NCI translational programs.

Funding Opportunity Goal(s)

To develop the means to cure as many cancer patients as possible and to control the disease in those patients who are not cured. Cancer Treatment Research includes the development and evaluation of improved methods of cancer treatment through the support and performance of both fundamental and applied laboratory and clinical research. Research is supported in the discovery, development, and clinical testing of all modes of therapy including: surgery, radiotherapy, chemotherapy, and biological therapy including molecularly targeted therapies, both individually and in combination.

Key Dates

Posted Date
December 16, 2024
Open Date (Earliest Submission Date)
April 19, 2025
Letter of Intent Due Date(s)

Not Applicable

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
May 19, 2025 May 19, 2025 Not Applicable November 2025 January 2026 April 2026
November 17, 2025 November 17, 2025 Not Applicable March 2026 May 2026 July 2026
May 18, 2026 May 18, 2026 Not Applicable November 2026 January 2027 April 2027
November 16, 2026 November 16, 2026 Not Applicable March 2027 May 2027 July 2027
May 17, 2027 May 17, 2027 Not Applicable November 2027 January 2028 April 2028
November 15, 2027 November 15, 2027 Not Applicable March 2028 May 2028 July 2028

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
November 16, 2027
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this notice of funding opportunity (NOFO) entitled "Toward Translation of Cancer Nanotechnology Interventions (TTNCI)" is to enable the translation of nanotechnology-based cancer interventions relying on nanoparticle formulations and/or nano-devices. Successful TTNCI projects will mature nanotechnology-based interventions that are designed for highly relevant cancer clinical objectives and address unmet clinical need. The projects should possess a strong potential to improve cancer diagnosis and/or treatment efficacy due to the combination of nanoparticle/nano-device structural design and/or therapeutic/diagnostic cargo which is delivered. The outcomes of TTNCI-supported projects should aid the development of mature nanotechnology interventions with efficacy exceeding the current standard of care for a given cancer indication. It is expected that successful TTNCI-supported projects, upon their completion, can qualify for Good Manufacturing Practice (GMP) materials synthesis and/or device fabrication and Good Laboratory Practice (GLP) and successfully compete for NCI Experimental Therapeutics (NExT) program and other NCI translational programs to continue a path towards the clinic. Projects supported by the TTNCI initiative will incorporate multi-disciplinary research in biology/oncology, chemistry, physics, and/or engineering and should rely on multidisciplinary leadership with one or more leading investigators having a pertinent clinical expertise.

Nanotechnology in the context of this NOFO. To be appropriate for this NOFO, the proposed nanotechnology approaches, materials, devices, and technologies should meet the following criteria:

  • The functional or active component(s) of devices or base materials either fabricated, assembled, or synthesized, must be at dimensions of 300 nm or less;
  • Materials used and/or proposed to be developed must be either synthetic or biologically based materials that are engineered to provide novel properties or modified functions due to their controlled assembly or synthesis at the nanoscale.

Nanoparticles and nano-devices that are/were in clinical trials. For nanoparticle constructs or nano-devices that are already in clinical trials, the proposed TTNCI project should involve a different cancer indication and/or different interventional approach than one investigated under the current/prior clinical trial.

Background

Potential of nanotechnology-based cancer interventions. Significant progress has been made in the synthesis and characterization of engineered nanoparticles and nano-devices for diagnosis and treatment of cancers and many cancer nanotechnology strategies have already moved into clinical trials and obtained FDA approval. The early development of nanomedicines has been conservative, selecting well-established nanoparticle constructs (i.e. liposomes) and combining them with FDA-approved small molecule drugs. Currently, efforts to encapsulate two or more drugs into one nanoparticle for their synergistic action as well as the use of other APIs such as nucleic acids, peptides, and antibodies are also being investigated. In parallel, materials scientists are studying a wide range of nanoparticle designs, possessing various mechanical, magnetic, optical, and biochemical properties. Such particles could perform not only as cargo (API) delivery vehicles, but also can contribute to improving treatment efficacy due to their material properties and structural design. Similarly, diagnostic strategies relying on in vivo imaging nanoparticles or in vitro nano-devices are being used for early disease detection, surgery assistance, and patient stratification to enhance treatment outcomes. Overall, these novel nanoparticle and nano-device designs combined with innovative therapeutic and diagnostic strategies have the potential to improve the effectiveness of nanotechnology interventions and integrate them into mainstream cancer care.

NCI has been supporting the development of nanotechnology for cancer using a multitude of funding mechanisms. . The information on these funding mechanisms as well as on general areas of research interests and currently funded grants can be found at http://nano.cancer.gov. The institute recognizes the importance of further support for translation of nanotechnology-based interventions and expects that, in the future, nanotechnology will become a significant part of clinical oncology.

Research Objectives for TTNCI Awards

General Expectations for TTNCI Projects. TTNCI awards are expected to produce advances in translational readiness of nanotechnology-based cancer interventions designed for highly relevant cancer clinical objectives. Significant advances are expected to be achieved in the overall capacity for employing these interventions as clinically viable cancer diagnostics and/or therapeutics. Each proposed TTNCI project is expected to focus within one or more of three selected areas: 1) Combination Therapy, 2) Immunotherapy, and 3) Imaging and Diagnostics. By the end of the TTNCI project, funded technologies should mature sufficiently to qualify for GMP materials synthesis and/or device fabrication and GLP evaluation studies and be well-positioned to compete for NCI translational programs including the NExT program.

Due to translational nature of TTNCI initiative, the innovative use of nanotechnology to address relevant cancer clinical objective is viewed as more significant than innovation in nanotechnology itself (e.g., development of new nanomaterials). Projects supported by the TTNCI initiative should incorporate multidisciplinary leadership with one or more leading investigators having a pertinent clinical expertise needed for the project. The proposed projects should also contain milestones to facilitate progress tracking.

Possible Research Directions. Examples of appropriate research areas are listed below. These examples are not meant to be comprehensive. Additional research foci are also encouraged, providing they are consistent with the general expectations stated above. For further details, see Section IV.2. Content and Form of Application Submission.

Research priorities of the proposed program were selected based on clinical challenges where nanotechnology has displayed a unique potential solution, as compared to other contemporary approaches. These priority areas include: 1) Combination Therapy, 2) Immunotherapy, and 3) Imaging and Diagnostics.

Combination Therapy

  • Expand the repertoire of delivered molecules;
  • Re-formulate highly potent, yet toxic drug loads;
  • Deliver two or more synergistic APIs (active pharmaceutical ingredients)) in precise ratios;
  • Deliver radionuclides for nanoparticle-based radiation therapies;
  • Leverage improved targeting strategies with proteolysis targeting chimeras (PROTACs);
  • Explore therapeutic advantage of combining antibody-drug-conjugates (ADCs) and nanoparticles;
  • Incorporate artificial intelligence to identify lead candidates in drug design. 

Immunotherapy

  • Deliver combinations of antigens and adjuvants;
  • Reverse immune-suppression;
  • Utilize nano-diagnostic tools to assess activity of immune cells;
  • Develop tools to understand and minimize immune-related adverse effects (irAEs);
  • Develop approaches for reprogramming of tumor microenvironment (TME);
  • Leverage specialized knowledge in lipid nanoparticles from COVID-19 vaccine development to design mRNA-based cancer therapies.

Imaging and Diagnostics

  • Enable and validate multi-modal imaging agents for in vivo diagnostic purposes;
  • Develop intra-operative imaging techniques;
  • Develop and validate in vitro nano-devices for improved cancer diagnosis and therapy outcome monitoring;
  • Combine diagnostic and therapeutic modalities into a multi-functional theranostic intervention strategies;
  • Develop strategies enabling stratification of patients to improve treatment outcomes;
  • Utilize image-guided strategies for improved therapeutic outcome;
  • Develop TME activatable imaging probes.

Tumor Types. All TTNCI applicants are expected to concentrate their proposed efforts on one or two rationally selected tumor types. For this FOA, a "tumor type" refers to either tumors of a specific tissue of origin or tumors with critical abnormalities in a particular molecular pathway(s) shared in cancers arising from a variety of tissues.

Annual Principal Investigators' Meeting

NCI holds an annual meeting of investigators funded through institute's nanotechnology programs with the purpose of sharing research progress and establishing collaborations. All investigators supported by this FOA are highly encouraged to attend this two-day meeting organized by NCI each year.

Additional Available Resources

Additional Available Resources

Applicants are encouraged to consider using, as appropriate, various relevant NCI-supported resources described below.

  • Nanomaterials characterization. The NCI recognizes that further development of nanotechnologies for oncology purposes will benefit greatly from a concerted and coordinated effort to characterize the wide range of nanoscale materials and devices. The NCI’s Nanotechnology Characterization Laboratory provides infrastructure support towards the uniform and consolidated characterization of these materials and devices and thus will aid the translation of nanotechnology-derived cancer therapeutics and diagnostics from the advanced discovery-phase to clinical environment.
  • Nanotechnology-related informatics. The NCI Center for Biomedical Informatics and Information Technology sponsors the Cancer Nanotechnology Laboratory data portal (caNanoLab). The caNanoLab is designed to facilitate sharing of nanomaterials data and to expedite and validate the use of nanomaterials in medicine.
  • NCI Experimental Therapeutics (NExT) program. The NCI Division of Cancer Therapy and Diagnosis (DCTD) operates the NExT Program to advance clinical practice and to bring improved therapies to patients with cancer. The NExT Program is not a grant mechanism; awardees do not receive direct funding; rather, the NCI may allocate various contract and grant resources toward the implementation and development of submitted projects. Successful applications need to describe a clear path to the clinic and potential benefit to patients.

Non-responsive Applications

This NOFO will NOT support projects that:

  • Involve discovery stage research on nanotechnology-based platforms with little to no prior evidence-based research;
  • Propose research utilizing nanoparticles or nano-devices which have been already approved by the FDA or are currently in clinical trials. It is acceptable, however to propose the project, which uses such nanoparticles or nano-devices for a different cancer indication and/or different interventional approach than approved or currently tested in clinical trials;
  • Involve clinical trials or in vivo studies in human subjects. However, projects involving in vitro studies of human samples are acceptable;
  • Propose only the use of naturally occurring materials (e.g., polysaccharides, proteins, viruses) that are not specifically engineered or modified for the intended function;
  • Focus on nanotechnology solutions for AIDS/HIV in the context of cancer.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to $475,000 in direct costs per year and need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 4 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized).

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

Facilities and Other Resources:

Under a heading "Nanomaterials Characterization and Animal Resources", provide a description of nanomaterials fabrication/synthesis and characterization facilities at your institution, your access to animal studies and the capacity to link to the capabilities of NCI’s Nanotechnology Characterization Laboratory (NCL).

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Specific Aims: Outline the specific goals of the project.

Research Strategy: The proposed project description must consist of the standard sub-sections: Significance, Innovation, and Approach and an additional "Milestones" sub-section (described below).

Significance

Project Scope and Emphasis. The proposed project should describe advanced pre-clinical development of nanotechnology-based cancer intervention which is designed for highly relevant cancer clinical objective and demonstrates strong potential for improving treatment and/or diagnosis effectiveness. These treatment improvements are expected to occur due to the combination of nanoparticle/nano-device structural design and/or therapeutic/diagnostic cargo which is delivered. The rationale for the clinical potential of described nanotechnology-based strategy should be clearly described in the project.

Innovation

In the Innovation sub-section, provide a comparison of the proposed nanotechnology-based intervention to available or possible classical approaches and/or currently used nanotechnology solutions. Discuss the potential advantage of the proposed approach and provide data supporting this advantage. Due to translational nature of TTNCI initiative, the innovative use of nanotechnology to address relevant cancer clinical objective is viewed as more significant than innovation in nanotechnology itself (e.g., development of new nanomaterials).

Approach

In the Approach sub-section, provide information pertaining to the following requirements.

1. Well Developed, Rigorous Project. Proposed projects are expected to focus on cancer intervention strategy with high clinical relevance. This relevance should be aligned with current needs of cancer diagnosis and treatment and be put into context of already existing interventions for given cancer indication. Projects need to be conceptually well developed and well supported by appropriate preliminary data from investigators’ laboratories with appropriate alternative strategies. . The preliminary data needs to demonstrate the efficacy of the proposed intervention in at least two animal models for applications proposing therapeutic or in vivo diagnostic strategies. This can include data from wide range of combinations of different animal species or tumor(s) originating from different cell lines in the same species. For applications involving in vitro diagnostic strategies, data can originate from experiments involving human samples. The scope of the proposed project should include physicochemical characterization, biodistribution, safety pharmacology, toxicokinetic/toxicodynamic studies, and additional efficacy confirmation studies in appropriate animal models (see section below: Selection of Animal Tumor Models). Furthermore, the proposed work should enable advanced optimization of the synthetic routes and process chemistry for proposed nanomedicines or fabrication processes for nano-devices. It is expected that by the end of the project, proposed technologies should mature sufficiently to qualify for GMP materials synthesis and/or device fabrication and GLP evaluation studies.

2. Interaction with the NCI's Nanotechnology Characterization Laboratory (NCL). The investigators are expected to work closely with NCL during their project and submit the initial batches of their nanomedicines for confirmatory physicochemical and biological characterization at the early stages of the project.

3. Data sharing. NCI supports the cancer Nanotechnology Laboratory data portal (caNanoLab; https://cananolab.nci.nih.gov/caNanoLab/). The investigators are required to deposit their data into caNanoLab. These data submission requirements are in line with the current NCI data management and sharing (DMS) policy.   

4. Selection of Tumor Types. The project may focus, as appropriate and justified, on one or two rationally selected tumor types or types of abnormalities. In selecting specific tumor types, TTNCI applicants are strongly encouraged to consider cancers that may strongly benefit from a nanotechnology approach and to take advantage of available resources with catalogs of clinical tumors that have been comprehensively characterized at the molecular genetics level (e.g., by programs such as The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and Cancer Genome Characterization Initiative (CGCI)). Additionally, applicants should consider the tumor type relative to its existing treatment and/or diagnostic paradigms and how their proposed approach could improve these for the tumor type or respective indication.

5. Selection of Animal Tumor Models. Describe the animal tumor models to be used in the proposed studies and explain why selected models carry the potential to predict the behavior in human subjects. The use of non-rodent species (large animals) in proposed studies is strongly encouraged, although not required;

6. Possible Research Directions. Examples of appropriate research directions are listed in Section I. The list is not meant to be comprehensive and additional directions/topics are also encouraged, providing they fit into the overall goals of TTNCI funding opportunity and conform to other requirements. Moreover, the listed examples are NOT mutually exclusive and are NOT meant to confine the scope of a project. Various directions may be combined into a single project, if appropriate.

Milestones

This sub-section is required for all applications. All applicants must describe here a set of discrete benchmarks that will allow unequivocal determination of the progress made towards the goals of the project. Milestones should be scientifically justified and well defined for each year of the project and be based on the proposed specific aims. Whenever feasible, milestones should provide quantitative benchmarks for comprehensively assessing the annual progress of the project. Milestones must not be simply a restatement of the specific aims. The specific aims describe the research goals of the project. The milestones should provide the means for assessing the progress made towards each aim and offer a timeline for it. The completion of these milestones will be used to judge the success of the proposed research on an individual project basis.

Examples of Milestones:

  • Assess the biodistribution of nanomedicine delivery to different organs by calculating the ratio of accumulation in tumor vs other organs
  • Quantify (and compare among different animal models, when applicable) dose-effect relationship
  • Quantify blood circulation half-life of proposed nanomedicine and compare it with half-life of its 'free' counterpart
  • Demonstrate that nanotechnology diagnostic imaging agent can resolve "x" cancer cells
  • Demonstrate the ability of a diagnostic construct to detect at least “x” specific proteins in blood with "y" sensitivity.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

  • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing Plan should address the sharing of nanomaterials data through the caNanoLab data portal. At least one scientifically qualified person is expected to be designated as the nanomaterial data sharing coordinator for each TTNCI project after an award has been made. All applications are expected to submit data to caNanoLab upon publication. Please refer to caNanoLab and Data Sharing - ICR - caNanoLab - NCI Wiki  for appropriate text.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply Application Guide.

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Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Mandatory Disclosure

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The emphasis and priority of this NOFO are on advancing translational readiness of nanotechnology-based cancer interventions. The priority will be given to innovative projects in advanced pre-clinical stage which use next generation nanoparticles or nano-devices for the development of clinically viable cancer interventions carrying strong potential of improving cancer treatment or diagnosis effectiveness.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Scored Review Criteria

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

 

Significance

  • Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance.
  • Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study.

Innovation

  • Evaluate the extent to which innovation influences the importance of undertaking the proposed research. Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field.
  • Evaluate whether the proposed work applies novel concepts, methods or technologies or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project.

Specific to this NOFO: 

  • Evaluate the clinical relevance of the proposed intervention. 
  • Evaluate the proposed nanotechnology-based strategy in context of its prospective improvement in therapy or diagnosis outcomes as compared to currently available and practiced non-nanotechnology approaches.
 

Approach

  • Evaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility).

Rigor:

  • Evaluate the potential to produce unbiased, reproducible, robust data.
  • Evaluate the rigor of experimental design and whether appropriate controls are in place.
  • Evaluate whether the sample size is sufficient and well-justified.
  • Assess the quality of the plans for analysis, interpretation, and reporting of results.
  • Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting.
  • For applications involving human subjects or vertebrate animals, also evaluate:
    • the rigor of the intervention or study manipulation (if applicable to the study design).
    • whether outcome variables are justified.
    • whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup.
    • whether the sample is appropriate and sufficiently diverse to address the proposed question(s).
  • For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research. Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science.

Feasibility:

  • Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work. For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances.
  • For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain an appropriately diverse population of participants. Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, racial, ethnic, and sex or gender categories.
  • For clinical trial applications, evaluate whether the study timeline and milestones are feasible.
 

Investigator(s)

Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.

Environment

Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.

Specific to this NOFO:

  • Evaluate whether the leadership of the project involves investigator(s) with pertinent clinical background.
 
Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

 

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects; 2) adequacy of protection against risks; 3) potential benefits to the subjects and others; 4) importance of the knowledge to be gained; and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, evaluate: 1) the justification for the exemption; 2) human subjects involvement and characteristics; and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

 

When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.

 

As applicable, evaluate the full application as now presented.

 

As applicable, evaluate the progress made in the last funding period.

 

As applicable, evaluate the appropriateness of the proposed expansion of the scope of the project.

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

 

For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.

 

Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

  1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
  2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Scientific/Research Contact(s)

Piotr Grodzinski, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3305
Email: [email protected]

Yicong Wu, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5634
Email: [email protected]

Peer Review Contact(s)

Mark G Caprara, PhD
Center for Scientific Review (CSR)
Telephone: 301-827-3076
Email: [email protected]

Financial/Grants Management Contact(s)

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.

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