Nanoparticle (NP) drug delivery systems can preferentially deliver and release a therapeutic cargo in the optimal dosage range at the site of disease, which in turn has the potential to result in improved therapeutic efficacy, reduced side effects and improved patient compliance. In fact, some of these improvements have already been realized in first generation nanotechnology-based therapeutics, including Doxil and Abraxane. Current research is now focused on engineering the next generation of nanoparticle therapeutics. Challenges in successful design are the numerous biological barriers that impede efficacious and efficient delivery of drugs to the site of the disease upon systemic administration. A thorough understanding of the impact of the physical parameters of the particlessize, shape, surface characteristics and deformability on biodistribution will aid in the rational design of nanoparticle therapeutics. Particle Replication In Nonwetting Templates is a novel method for the molding of shape-specific particles at the nanometer scale developed by DeSimone and coworkers at the University of North Carolina at Chapel Hill. PRINT offers an unprecedented opportunity to study the problems associated with nanoparticle delivery and, more importantly, offers a versatile platform to engineer solutions to these problems. In this project, we will exploit the advantages of PRINT to generate "calibration quality" nano-tools to define the geometric (size, shape), surface (zeta potential, stealthing ligands) and deformability limitations associated with the delivery of drugs using different dosage forms (IV and IP) (Aim 1). In addition, we will use PRINT particles as a platform to test biomimetic strategies for the evasion of clearance by the mononuclear phagocytic system (MPS) (Aim 2). Finally, we will use the versatility of PRINT to address the role of particle characteristics on site specific targeting and controlled release of drugs in the tumor bed to improve therapeutic index (Aim 3).

Public Health Relevance

The utilization of nanocarriers for the delivery of therapeutics has led to a significant decrease in the toxicity of chemotherapeutics and point to the potential of nanoparticle based therapies to improve cancer treatment. Current research, including the research proposed in this application, is focused on developing nanoparticle carriers that can improve the therapeutic efficacy as well as further lower the toxicity of small molecule cytotoxins as well as allow for the effective delivery of fragile biologies like siRNA.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-GRB-S)
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University of North Carolina Chapel Hill
Chapel Hill
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Lucas, Andrew T; O'Neal, Sara K; Santos, Charlene M et al. (2016) A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues. J Pharm Biomed Anal 119:122-9
Kai, Marc P; Brighton, Hailey E; Fromen, Catherine A et al. (2016) Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance. ACS Nano 10:861-70
Roode, Luke E; Brighton, Hailey; Bo, Tao et al. (2016) Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties. Nanomedicine 12:1053-62
Miao, Lei; Liu, Qi; Lin, C Michael et al. (2016) Targeting Tumor-associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors. Cancer Res :
Li, Chengwen; Wu, Shuqing; Albright, Blake et al. (2016) Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer. Mol Ther 24:53-65
DeSimone, Joseph M; Mecham, Sue J; Farrell, Crista L (2016) Organic Polymer Chemistry in the Context of Novel Processes. ACS Cent Sci 2:588-597
Lecaros, Rumwald Leo G; Huang, Leaf; Lee, Tsai-Chia et al. (2016) Nanoparticle Delivered VEGF-A siRNA Enhances Photodynamic Therapy for Head and Neck Cancer Treatment. Mol Ther 24:106-16
Lu, Yao; Miao, Lei; Wang, Yuhua et al. (2016) Curcumin Micelles Remodel Tumor Microenvironment and Enhance Vaccine Activity in an Advanced Melanoma Model. Mol Ther 24:364-74
Sambade, Maria; Deal, Allison; Schorzman, Allison et al. (2016) Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT(®) nanoparticle formulation against non-small-cell lung cancer brain metastases. Nanomedicine (Lond) 11:1947-55
Rose, Tracy L; Deal, Allison M; Ladoire, Sylvain et al. (2016) Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer. Bladder Cancer 2:405-413

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