Recently, we have developed nanocrystals capable of delivering anticancer drugs. These nanocrystals with possess low toxicity, high drug loading ratio, and overcome multidrug resistance (MDR) in cancer cells in vitro and in vivo. The overall goal of this research proposal is to further develop and investigate multifunctional nanocrystals for MDR cancer therapy. The scientific basis for this proposal originated from our three-phase nanoparticle engineering (3PNE) method recently developed, which includes phase 1, amorphous precipitate;phase 2, hydrated amorphous aggregate;and phase 3, stabilized nanocrystals (NCs). The 3PNE has been applied to the development of rod-shaped NCs for effective anticancer drug delivery. To achieve this goal, we propose three aims:
specific aim 1, to examine the mechanisms of the NCs for their ability to enhance physical stability, overcome MDR, and their in vivo behavior;
specific aim 2, to develop NCs that carry target ligands to deliver PTX to tumor;
and specific aim 3, to establish the NCs for co-delivering a hydrophobic drug (i.e., Paclitaxel) and a hydrophilic anti-cancer drug (i.e., 5-fluorouracil) to synergistically kill tumor cells through different cellular mechanisms. Accomplishing these specific aims will further develop efficient nano-drug carriers for the treatment of cancer, particularly MDR cancer.

Public Health Relevance

This project is relevant to cancer therapy in public health in two ways. First, it has the potential to develop novel nanocrystals (NCs) as an anticancer drug carrier for the efficient treatment of multidrug resistance (MDR) in cancer. Moreover, if successful, the development of new NCs in this proposal has the potential to deliver hydrophobic drugs for the treatment other diseases.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Gene and Drug Delivery Systems Study Section (GDD)
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Fu, Yali
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University of North Carolina Chapel Hill
Schools of Pharmacy
Chapel Hill
United States
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Ma, Yan; Liu, Dan; Wang, Dun et al. (2014) Combinational delivery of hydrophobic and hydrophilic anticancer drugs in single nanoemulsions to treat MDR in cancer. Mol Pharm 11:2623-30
Wang, Yongjun; Wang, Dun; Fu, Qiang et al. (2014) Shape-controlled paclitaxel nanoparticles with multiple morphologies: rod-shaped, worm-like, spherical, and fingerprint-like. Mol Pharm 11:3766-71
Wang, Yongjun; Liu, Dan; Zheng, Qingchuan et al. (2014) Disulfide bond bridge insertion turns hydrophobic anticancer prodrugs into self-assembled nanomedicines. Nano Lett 14:5577-83
Tang, Jingling; Wang, Yongjun; Wang, Dun et al. (2013) Key structure of brij for overcoming multidrug resistance in cancer. Biomacromolecules 14:424-30
Wang, Dun; Tang, Jingling; Wang, Yongjun et al. (2013) Multifunctional nanoparticles based on a single-molecule modification for the treatment of drug-resistant cancer. Mol Pharm 10:1465-9
Tang, Jingling; Fu, Qiang; Wang, Yongjun et al. (2013) Vitamin E reverses multidrug resistance in vitro and in vivo. Cancer Lett 336:149-57