Curcumin, a yellow polyphenol compound found in the Indian spice turmeric (Curcuma longa) demonstrates potent anti-cancer effects against a wide variety of human tumor models in preclinical studies. A major pitfall for the application of curcumin to human cancer therapy has been its limited systemic bioavailability, such that the few clinical trials conducted so far had administered """"""""mega"""""""" doses (8-10 grams) of free curcumin daily to patients in order to yield detectable levels. These high dosages significantly affect patient compliance and have stymied the application of this promising, and relatively non-toxic, agent to most visceral malignancies that would mandate high plasma levels of the active therapeutic. A novel nanoparticle encapsulated formulation of curcumin (nanocurcumin) has been engineered which bypasses the bioavailability pitfall of this compound, and enables strikingly higher circulating and tissue levels upon parenteral administration. Nanocurcumin causes significant growth reduction of subcutaneous and orthotopic pancreatic cancer xenografts, and abrogates systemic metastases when co-administered with gemcitabine in a spontaneously metastatic animal model. The studies proposed herein have the overarching goal of performing the efficacy, pharmacokinetics, and toxicity data required for filing an investigational new drug (IND) application with the USFDA. To this effect, nanocurcumin (as single agent or in combination with gemcitabine) will be tested in a panel of low-passage gemcitabine-resistant patientderived orthotopic xenografts (Aim 1) and in a uniformly lethal genetically engineered mouse model (Aim 2), and will undergo """"""""regulatory grade"""""""" in vitro and in vivo toxicology testing by the federally-funded Nanotechnology Characterization Laboratory (NCL) (Aim 3), in preparation for a pre-IND application. Two hypothesis-driven aims that integrate unique CCNE resources will also be pursued, including the effects of nanocurcumin on vaccine efficacy and quantifiable measures of cellular immune response (Aim 4;in collaboration with Project 3) and engineering the next generation of active-targeted antibody-conjugated nanocurcumin (Aim 6;in collaboration with the Nanoparticle Engineering and the Validation Cores).

Public Health Relevance

The clinical translation of the promising anti-cancer agent curcumin has been hampered due to poor absorption from the gut. We have generated a nanocurcumin formulation that, for the first time, bypasses this major pitfall, and has the potential to enable widespread application of curcumin to cancer therapy. The studies proposed herein are focused on generating the efficacy and toxicity required to begin clinical trials.

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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Johns Hopkins University
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Huang, Xinglu; Chisholm, Jane; Zhuang, Jie et al. (2017) Protein nanocages that penetrate airway mucus and tumor tissue. Proc Natl Acad Sci U S A 114:E6595-E6602
Dawidczyk, Charlene M; Russell, Luisa M; Hultz, Margot et al. (2017) Tumor accumulation of liposomal doxorubicin in three murine models: Optimizing delivery efficiency. Nanomedicine 13:1637-1644
Banerjee, Sangeeta R; Foss, Catherine A; Horhota, Allen et al. (2017) 111In- and IRDye800CW-Labeled PLA-PEG Nanoparticle for Imaging Prostate-Specific Membrane Antigen-Expressing Tissues. Biomacromolecules 18:201-209
Shin, Soo Hyun; Kadayakkara, Deepak K; Bulte, Jeff W M (2017) In Vivo (19)F MR Imaging Cell Tracking of Inflammatory Macrophages and Site-specific Development of Colitis-associated Dysplasia. Radiology 282:194-201
Williford, John-Michael; Archang, Maani M; Minn, Il et al. (2016) Critical Length of PEG Grafts on lPEI/DNA Nanoparticles for Efficient in Vivo Delivery. ACS Biomater Sci Eng 2:567-578
Stark, Alejandro; Shin, Dong Jin; Pisanic 2nd, Thomas et al. (2016) A parallelized microfluidic DNA bisulfite conversion module for streamlined methylation analysis. Biomed Microdevices 18:5
Yan, Lesan; Li, Xingde (2016) Biodegradable Stimuli-Responsive Polymeric Micelles for Treatment of Malignancy. Curr Pharm Biotechnol 17:227-36
Huang, Yu-Ja; Hoffmann, Gwendolyn; Wheeler, Benjamin et al. (2016) Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells. Sci Rep 6:21583
Yu, Tao; Chisholm, Jane; Choi, Woo Jin et al. (2016) Mucus-Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces. Adv Healthc Mater 5:2745-2750
Mukherjee, Amarnath; Kumar, Binod; Hatano, Koji et al. (2016) Development and Application of a Novel Model System to Study ""Active"" and ""Passive"" Tumor Targeting. Mol Cancer Ther 15:2541-2550

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