Toward Translation of Nanotechnology Cancer Interventions (TTNCI; R01 Clinical Trial Not Allowed)

Toward Translation of Nanotechnology Cancer Interventions (TTNCI; R01 Clinical Trial Not Allowed) is sponsored by National Cancer Institute (NCI), National Institutes of Health (NIH). This opportunity supports mission-aligned projects and measurable outcomes.

PAR-25-336: Toward Translation of Nanotechnology Cancer Interventions (TTNCI; R01 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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) R01 Research Project Grant March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) 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.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description 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. 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.

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.

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.

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 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 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. Not Allowed: Only accepting applications that do not propose clinical trials. Need help determining whether you are doing a clinical trial?

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. Application budgets are limited to $475,000 in direct costs per year and need to reflect the actual needs of the proposed project. 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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

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

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

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). 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. 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.

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.

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.

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