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使用脂质体对长春新碱 (Vincristine) 硫酸盐共轭的金纳米粒子的递送： 提高抗肿瘤疗效的光响应纳米载体

 

Authors Liu Y, He M, Niu MM, Zhao YQ, Zhu YZ, Li ZH, Feng NP

Published Date April 2015 Volume 2015:10 Pages 3081—3095

DOI http://dx.doi.org/10.2147/IJN.S79550

Received 18 December 2014, Accepted 31 January 2015, Published 22 April 2015

Abstract: Rapid drug release at the specific site of action is still a challenge for antitumor therapy. Development of stimuli-responsive hybrid nanocarriers provides a promising strategy to enhance therapeutic effects by combining the unique features of each component. The present study explored the use of drug–gold nanoparticle conjugates incorporated into liposomes to enhance antitumor efficiency. A model drug, vincristine sulfate, was physically conjugated with gold nanoparticles and verified by UV-visible and fourier transform infrared spectroscopy, and differential scanning calorimetry. The conjugates were incorporated into liposomes by film dispersion to yield nanoparticles (113.4 nm) with light-responsive release properties, as shown by in vitro release studies. Intracellular uptake and distribution was studied in HeLa cells using transmission electron microscopy and confocal laser scanning microscopy. This demonstrated liposome internalization and localization in endosomal–lysosomal vesicles. Fluorescence intensity increased in cells exposed to UV light, indicating that this stimulated intracellular drug release; this finding was confirmed by quantitative analyses using flow cytometry. Antitumor efficacy was evaluated in HeLa cells, both in culture and in implants in vivo in nude mice. HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. Furthermore, treatment with the prepared liposomes coupled with UV light exposure produced greater antitumor effects in nude mice and reduced side effects, as compared with free vincristine sulfate.
Keywords: vincristine sulfate, vincristine sulfate–gold nanoparticle conjugates, liposomes, antitumor efficiency, light triggered drug release






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