RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway

• Published in: Nanoscale research letters Vol. 15; no. 1
• Main Authors: Tang, Xiaolong, Li, Amin, Xie, Chunmei, Zhang, Yinci, Liu, Xueke, Xie, Yinghai, Wu, Binquan, Zhou, Shuping, Huang, Xudong, Ma, Yongfang, Cao, Weiya, Xu, Ruyue, Shen, Jing, Huo, Zhen, Cai, Shuyu, Liang, Yong, Ma, Dong
• Format: Journal Article
• Language: English
• Published: New York Springer US 26.03.2020; Springer Nature B.V
• Subjects: Biological effects; Chemistry and Materials Science; Materials Science; Molecular Medicine; Nano Express; Nanochemistry; Nanoscale Science and Technology; Nanotechnology; Nanotechnology and Microengineering; Polymers; Nanoparticles; Dactolisib (BEZ235); Hepatocellular carcinoma; HIF-1α; Radiosensitivity
• ISSN: 1556-276X; 1931-7573; 1556-276X
• DOI: 10.1186/s11671-020-3289-z

Polymer materials encapsulating drugs have broad prospects for drug delivery. We evaluated the effectiveness of polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG) encapsulation and release characteristics of PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235). We proposed a strategy for targeting radiosensitization of liver cancer cells. The biocompatibility, cell interaction, and internalization of Glypican-3 (GPC3) antibody-modified, BEZ235-loaded PLGA-PEG nanoparticles (NP-BEZ235-Ab) in hepatoma cells in vitro were studied. Also, the cell killing effect of NP-BEZ235-Ab combined with γ-ray cell was evaluated. We used confocal microscopy to monitor nanoparticle-cell interactions and cellular uptake, conducted focus-formation experiments to analyze the synergistic biological effects of NP-BEZ235-Ab and priming, and studied synergy in liver cancer cells using molecular biological methods such as western blotting. We found that PLGA-PEG has good loading efficiency for BEZ235 and high selectivity to GPC3-positive HepG2 liver cancer cells, thus documenting that NP-BEZ235-Ab acts as a small-molecule drug delivery nanocarrier. At the nominal concentration, the NP-BEZ235-Ab nanoformulation synergistically kills liver cancer cells with significantly higher efficiency than does the free drug. Thus, NP-BEZ235-Ab is a potential radiosensitizer. Graphical Abstract