Division of Cardiovascular Diseases Strategic Plan
Goals in Enabling Technologies and Methodologies for Cardiovascular Disease
1.6. Apply nanoparticle-based targeted agents to diagnose and treat cardiovascular diseases
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Nanoparticles offer the opportunity for major advance in CV diagnosis and treatment, with the potential for highly specific delivery of a wide variety of imaging and therapeutic agents. Nanoparticles may be multifunctional, allowing them to combine targeting elements, imaging agents, and/or therapeutic payloads. Such multi-purpose payloads are termed “theranostic”. The tuning of additional factors such as adhesive properties, cell penetrating tags, and cargo releasing mechanisms is also possible. Most nanoparticle studies have been performed in cell culture and in small animal models. In order to move nanoparticle-based agents into clinical practice, the field needs to move towards more clinically relevant large animal models. Toxicity and biodistribution studies need to be performed early enough in the development cycle so that efforts are not wasted on nanoparticles with no clinical potential. For clinically promising agents, Good Manufacturing Practices (GMP) (or near GMP) manufacturing facilities will be needed in order to carry out preclinical studies that can receive FDA approval.
Strategies to Accomplish this Goal May Entail:
- Identify optimal molecular species for targeting nanoparticles to disease moieties in animal models. An example may be to optimize ligands to detect different stages of aortic aneurysm development and differentiate stable from unstable aneurysms.
- Test the efficacy of nanoparticles for imaging disease processes, delivering therapy, and monitoring disease progression and regression. An example may be the use of theranostic nanoparticles targeted to cell surface markers on the vasa vasorum of atherosclerotic plaque to track and inhibit angiogenesis .
- Improve the signal-to-noise ratio for nanoparticle imaging agents by modulating targeting elements, imaging payload, and plasma clearance. An example may be to modify nanoparticle surface and/or structure to modify uptake by the reticuloendothelial system.
- Design nanoparticle structure/therapeutic payload combinations to optimize disease treatment and release drugs in a programmable or sub-cellular-specific fashion. An example may be the development of nanoparticles to deliver siRNA intracellularly and efficiently to a targeted cell population to reduce inflammation.
- Confirm efficacy in clinically relevant large animal disease models. An example may be to assess plaque development and regression in response to theranostic nanoparticles in atherosclerotic animal models.
- Assess toxicity of agents, including development of high throughput screening (HTS) methods for initial screening of candidate nanoparticles.
- Develop GMP processes to meet requirements for FDA approval, and achieve the scale necessary for clinical studies.
- Perform initial safety studies in humans.
- Determine the efficacy of nanoparticles as imaging and therapeutic agents in clinical studies/trials.