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

Xiaolong Tang; Amin Li; Chunmei Xie; Yinci Zhang; Xueke Liu; Yinghai Xie; Binquan Wu; Shuping Zhou; Xudong Huang; Yongfang Ma; Weiya Cao; Ruyue Xu; Jing Shen; Zhen Huo; Shuyu Cai; Yong Liang; Dong Ma

doi:10.1186/s11671-020-3289-z

Nanoscale Research Letters (Mar 2020)

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

Xiaolong Tang,
Amin Li,
Chunmei Xie,
Yinci Zhang,
Xueke Liu,
Yinghai Xie,
Binquan Wu,
Shuping Zhou,
Xudong Huang,
Yongfang Ma,
Weiya Cao,
Ruyue Xu,
Jing Shen,
Zhen Huo,
Shuyu Cai,
Yong Liang,
Dong Ma

Affiliations

Xiaolong Tang: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Amin Li: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Chunmei Xie: Blood Transfusion Department, Guangzhou 8th People’s Hospital, Guangzhou Medical University
Yinci Zhang: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Xueke Liu: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Yinghai Xie: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Binquan Wu: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College
Shuping Zhou: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Xudong Huang: Department of Interventional, Affiliated Oriental Hospital, Anhui University of Technology
Yongfang Ma: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Weiya Cao: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Ruyue Xu: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Jing Shen: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Zhen Huo: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Shuyu Cai: Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Anhui University of Science and Technology
Yong Liang: Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second Hospital
Dong Ma: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University

DOI: https://doi.org/10.1186/s11671-020-3289-z
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 16

Abstract

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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. Graphical Abstract

Published in Nanoscale Research Letters

ISSN: 1931-7573 (Print); 1556-276X (Online)
Publisher: SpringerOpen
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.springer.com/journal/11671

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