Enhanced cellular uptake of folic acid–conjugated PLGA–PEG nanoparticles loaded with vincristine sulfate in human breast cancer

Abstract

The aim of this paper is to evaluate the cellular uptake of vincristine sulfate-loaded poly(lactic-co-glycolic acid)–polyethylene glycol (PLGA–PEG) nanoparticles with the folic acid modification (PLGA–PEG–folate NPs). PLGA–PEG–folate NPs were prepared using a water–oil–water emulsion solvent evaporation method. The particle size, surface morphology, drug encapsulation efficiency, and the drug release behavior were investigated. The NPs exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. Internalization of the NPs labeled with coumarin- 6 by MCF-7 (Michigan Cancer Foundation-7) human breast cancer cells was quantitatively measured by microplate reader, and qualitatively analyzed by fluorescent microscopy and confocal laser scanning microscopy. The results showed PLGA–PEG–folate NPs achieved significantly higher cellular uptake in the folic acid receptor overexpressed MCF-7 cells, compared to PLGA–mPEG NPs without the folic acid modification. Due to the enhanced cellular uptake, PLGA–PEG–folate NPs displayed the highest cytotoxicity. Judged by IC₅₀ after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface modification could be 1.52 times, 3.91 times higher than that of PLGA–mPEG NPs and free vincristine sulfate, respectively.

Keywords::

• Cellular uptake
• folic acid
• conjugation
• PLGA–PEG
• nanoparticle
• vincristine sulfate

Acknowledgments

We would like to thank Drs. Tian Lan and Wen Zhou (School of Pharmacy, Shanghai Jiao Tong University) for their advice on synthesis.

Declaration of interest

This work was supported by the National Natural Science Foundation of China (grant no. 30973644), the National Basic Research Program of China (973 Program), No. 2007CB936004, and the National comprehensive technology platforms for innovative drug (R&D, 2009ZX09301-007). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.