谷胱甘肽
白藜芦醇
丁硫胺
癌细胞
化学
内化
药物输送
毒性
体外
抗氧化剂
癌症研究
药理学
细胞
癌症
生物化学
医学
生物
酶
内科学
有机化学
作者
Marco Palminteri,Nilesh Kumar Dhakar,Alessandra Ferraresi,Fabrizio Caldera,Chiara Vidoni,Francesco Trotta,Ciro Isidoro
出处
期刊:Nanotheranostics
[Ivyspring International Publisher]
日期:2021-01-01
卷期号:5 (2): 197-212
被引量:26
摘要
Smart drug delivery systems are required for the site-specific drug targeting to enhance the therapeutic efficiency of a drug. Resveratrol (RV) is a polyphenolic compound with anti-cancer activity. However, its poor aqueous solubility and non-selectivity are the major challenges for its employment in cancer therapy. In this work, we present the synthesis of RV-loaded glutathione responsive cyclodextrin nanosponges (RV-GSH-NSs) to improve the therapeutic efficiency and selective delivery of RV. The drug loading and encapsulation efficiency were 16.12% and 80.64%, respectively. The in vitro release profile confirmed that RV release was enhanced in response to external glutathione (GSH). Nude NSs were not toxic per se to human fibroblasts when administered for up to 72 h at the highest dose. Cell internalization studies confirmed that RV-GSH-NSs were preferentially up-taken by tumor cells compared to non-tumorigenic cells. Accordingly, RV showed selective toxicity to cancer cells compared to normal cells. GSH depletion by buthionine sulfoximine, a potent inhibitor of its synthesis, reflected in a significant decrease of the NSs accumulation, and consequently resulted in a drastic reduction of RV-mediated toxic effects in cancer cells. These findings demonstrate that GSH- responsive NSs represent an effective delivery system for targeting cancer cells by harnessing the differential tumor characteristics in terms of redox status in parallel with the limitation of side effects toward normal cells.
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