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This Funding Opportunity Announcement (FOA) will support innovative research in image-guided drug delivery (IGDD) for cancer and other diseases. The overarching goals of this FOA are to support the development of quantitative in vivo imaging methods for IGDD across different physical and physiological resolution scales in order to interrogate tumor-drug interaction, study biodistribution, pharmacokinetics, pharmacodynamics and therapeutic response. Studies that are directed towards translation of IGDD technology to patient care will be considered appropriate for this FOA. This FOA will support research in development of integrated imaging-based platforms for multifunctional and multiplexed drug delivery systems for therapy.Background
Cancer is primarily characterized by the uncontrolled proliferation of cells and their ability to metastasize. Despite significant advancements in the fight against cancer, it remains a challenging medical problem, particularly in the lungs, breast, liver, prostate, pancreas, and brain. To date, systemic chemotherapy is a common approach to the chronic management of cancer in patients. However, systemic toxicity is a major drawback, limiting the utility and effectiveness of chemotherapeutics. Recent research efforts in the development of drug delivery systems have concentrated on targeted delivery and controlled release of the drug or other agents in the tumor in order to increase the therapeutic ratio. Oncologic IGDD is a therapeutic method where tumor localization and drug delivery are guided and monitored through noninvasive imaging. A full implementation of IGDD will require drugs that can be imaged or identified in the body as they enter the blood stream, are localized at the target, and are then released or otherwise activated to provide focal treatment. The goal in IGDD is to optimize local delivery of the therapeutic pharmaceutical to the target tissue and provide microanatomical and functional imaging feedback on the therapeutic process(es), including during treatment and monitoring.
This FOA is one of a series of initiatives that reflect the comprehensive effort by the National Cancer Institute, Cancer Imaging Program, to advance the various aspects of image-guided interventions. The impetus for this FOA is to address the challenges associated with therapeutic delivery and the study of effectiveness and efficacy. Recent studies that focus on the engineering of targeted delivery systems and advanced imaging methodologies have shown the ability to quantify location and magnitude of targeted delivery. For instance, recent advances in applications of nanotechnologies to cancer have led to the development of nanocarriers that can deliver imaging contrast agents and therapeutics at the sub-cellular level (NCI Alliance for Nanotechnology in Cancer; http://nano.cancer.gov/). Furthermore, these nanoparticles may be functionalized to target certain tumors, and could be activated upon absorption of external energies or in response to chemical reactions. Nanoparticle constructs have the capability to be functionalized, to carry multiple imaging, targeting, and therapeutic moieties, to be multiplexed, to respond to various biological signals in real-time, thus making them particularly suitable for IGDD. Despite significant accomplishments in applications of nanotechnology for cancer, barriers remain for successful implementation of IGDD as a clinical solution. These translational barriers relate to variations in formulations and in vivo stability of nanoparticles, and limited data on the fate and toxicity of nanocarriers once they enter the body. Quantitative imaging may prove to be an invaluable tool to help overcome some of the barriers associated with the clinical translation of nanocarrier-enabled drug delivery in cancer as it will help provide quantitative data on nanoparticle behavior and distribution in vivo. Quantitative imaging methods may be used for target characterization (detection, localization, and pathology) to study the pharmacokinetics (PK) and pharmacodynamics (PD) of therapeutic uptake and efficacy, respectively, to determine the biodistribution and therapeutic effects across different spatial and functional resolution scales (molecular to organ level). Imaging and drug delivery systems supported through this FOA are not limited to nanotechnology based systems and they may include a variety of approaches including catheter based delivery, extracorporeal-triggered delivery and release through the use of eletromganetic or ultrasonic radiation systems, and biologically targeted small molecules labeled with imaging radioactive conjugates.Specific Research Objectives
This FOA will support research in IGDD. Of particular interest are studies that address translational barriers, including variations of in vivo formulations, lack of quantitative imaging data on in vivo biodistribution and PK/PD. Furthermore, studies that address interventions of early cancer and rare cancers are encouraged.
Examples of research supported by this FOA include, but are not limited to, the following areas:
- Development of multi-functional and multiplexed imaging and therapeutic delivery systems for specific types of cancer. The therapeutic payload may be a drug, cocktail of drugs, or sensitizers to external therapies, such as radiation or heat;
- Development of multifunctional and multiplexed IGDD systems that incorporate the active pharmaceutical ingredients (APIs) into the original design of the delivery nanovector;
- Development of imaging methods as quantitative, and when appropriate, real-time assays for biophysical and biochemical characterization of the drug delivery process, including biodistribution, PK/PD, as well as target characterization, dosimetry, and toxicology across different temporal and spatial resolution scales;
- Development of innovative reference standards for image-guided drug delivery;
- Validation of imaging assays of drug delivery using standard models, including histology and quantitative autoradiography;
- Development and validation of the controlled release of multifunctional imaging payloads that is indicative of the target localization and the therapeutic process;
- Image-guidance technologies for increasing the range and quality of drug delivery systems that will also improve image interpretation;
- Studies that use non-human primates or other large animal models in pre-clinical validation and toxicology of IGDD vectors; and
- Studies that are directed towards translation of IGDD technology into the clinic.
Applicants are encouraged to use the multiple Program Director/Principal Investigator (PD/PI) grant model to meet the required imaging and in vivo drug delivery components. The involvement of expertise in experimental or clinical oncology at an early stage of the investigation is also encouraged. Participation of partners from the commercial sector is encouraged.
Moreover, collaborative activities are encouraged with an existing NCI-funded center or consortium (i.e., with U01 or U54 awardees), as pertinent to a broader consensus for the proposed translational research methods or the creation of public resources for translational research.
Because the aim of this FOA is to support research in overcoming translational barriers to IGDD, large clinical trials will not be considered appropriate for this FOA.
For more inforation and to apply, click here.