Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 11, Issue 7, Pages 1247-1260Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2015.2068
Keywords
Nanomedicine; Simvastatin; CA-PLGA; Cancer Nanotechnology; Drug Delivery
Funding
- National Natural Science Foundation of China [31270019, 51203085]
- Program for New Century Excellent Talents in University [NCET-11-0275]
- China Postdoctoral Science Foundation [2012M520242]
- Natural Science Foundation of Guangdong Province [S2012040006820, S2012010010046]
- Science, Technology and Innovation Commission of Shenzhen Municipality [JCYJ20120616213729920, KQC201105310021A, JCYJ20120614191936420, JC201005270308A]
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A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.
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