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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA149387-02
Application #
8321471
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Fu, Yali
Project Start
2011-08-17
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$307,100
Indirect Cost
$99,600
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Luo, Cong; Sun, Jin; Sun, Bingjun et al. (2016) Facile Fabrication of Tumor Redox-Sensitive Nanoassemblies of Small-Molecule Oleate Prodrug as Potent Chemotherapeutic Nanomedicine. Small 12:6353-6362
Satterlee, Andrew B; Huang, Leaf (2016) Current and Future Theranostic Applications of the Lipid-Calcium-Phosphate Nanoparticle Platform. Theranostics 6:918-29
Miao, Lei; Newby, Jay M; Lin, C Michael et al. (2016) The Binding Site Barrier Elicited by Tumor-Associated Fibroblasts Interferes Disposition of Nanoparticles in Stroma-Vessel Type Tumors. ACS Nano :
Xiong, Yang; Zhao, Yi; Miao, Lei et al. (2016) Co-delivery of polymeric metformin and cisplatin by self-assembled core-membrane nanoparticles to treat non-small cell lung cancer. J Control Release 244:63-73
Miao, Lei; Liu, Qi; Lin, C Michael et al. (2016) Targeting Tumor-associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors. Cancer Res :
Luo, Cong; Miao, Lei; Zhao, Yi et al. (2016) A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA. Biomaterials 102:239-48
Liu, Hongzhuo; Ma, Yan; Liu, Dan et al. (2016) The Effect of Surfactant on Paclitaxel Nanocrystals: An In Vitro and In Vivo Study. J Biomed Nanotechnol 12:147-53
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
Goodwin, Tyler J; Zhou, Yingqiu; Musetti, Sara N et al. (2016) Local and transient gene expression primes the liver to resist cancer metastasis. Sci Transl Med 8:364ra153

Showing the most recent 10 out of 32 publications