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

Authors
  • Tang, Xiaolong1
  • Li, Amin1
  • Xie, Chunmei2
  • Zhang, Yinci1
  • Liu, Xueke1
  • Xie, Yinghai1
  • Wu, Binquan3
  • Zhou, Shuping1
  • Huang, Xudong4
  • Ma, Yongfang1
  • Cao, Weiya1
  • Xu, Ruyue1
  • Shen, Jing1
  • Huo, Zhen1
  • Cai, Shuyu1
  • Liang, Yong5
  • Ma, Dong6
  • 1 Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China , Huainan (China)
  • 2 Guangzhou Medical University, Guangzhou, 510632, People’s Republic of China , Guangzhou (China)
  • 3 The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China , Bengbu (China)
  • 4 Anhui University of Technology, Huainan, 232003, People’s Republic of China , Huainan (China)
  • 5 Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second Hospital, Huai’an, 223002, People’s Republic of China , Huai’an (China)
  • 6 Jinan University, Guangzhou, 510632, People’s Republic of China , Guangzhou (China)
Type
Published Article
Journal
Nanoscale Research Letters
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Mar 26, 2020
Volume
15
Issue
1
Identifiers
DOI: 10.1186/s11671-020-3289-z
Source
Springer Nature
Keywords
License
Green

Abstract

AbstractPolymer 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

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