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The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway.
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.
Afiliação
  • Tang X; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Li A; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Xie C; Blood Transfusion Department, Guangzhou 8th People's Hospital, Guangzhou Medical University, Guangzhou, 510632, People's Republic of China.
  • Zhang Y; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Liu X; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Xie Y; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Wu B; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People's Republic of China.
  • Zhou S; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Huang X; Department of Interventional, Affiliated Oriental Hospital, Anhui University of Technology, Huainan, 232003, People's Republic of China.
  • Ma Y; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Cao W; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Xu R; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Shen J; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Huo Z; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Cai S; Huainan First People's Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology, Huainan, 232001, People's Republic of China.
  • Liang Y; Huai'an Hospital Affiliated of Xuzhou Medical College and Huai'an Second Hospital, Huai'an, 223002, People's Republic of China. harcyyly@163.com.
  • Ma D; Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, People's Republic of China. tmadong@jnu.edu.cn.
Nanoscale Res Lett ; 15(1): 63, 2020 Mar 26.
Article em En | MEDLINE | ID: mdl-32219609
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Nanoscale Res Lett Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Nanoscale Res Lett Ano de publicação: 2020 Tipo de documento: Article