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.

Details

Title
The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway
Author
Tang, Xiaolong 1   VIAFID ORCID Logo  ; Li, Amin 1 ; Xie Chunmei 2 ; Zhang Yinci 1 ; Liu Xueke 1 ; Xie Yinghai 1 ; Wu Binquan 3 ; Zhou, Shuping 1 ; Huang, Xudong 4 ; Ma Yongfang 1 ; Cao Weiya 1 ; Xu Ruyue 1 ; Shen, Jing 1 ; Huo Zhen 1 ; Cai Shuyu 1 ; Liang, Yong 5 ; Ma, Dong 6 

1  Anhui University of Science and Technology, Huainan First People’s Hospital and First Affiliated Hospital of Medical School, Huainan, People’s Republic of China (GRID:grid.440648.a) (ISNI:0000 0001 0477 188X) 
2  Guangzhou Medical University, Blood Transfusion Department, Guangzhou 8th People’s Hospital, Guangzhou, People’s Republic of China (GRID:grid.410737.6) (ISNI:0000 0000 8653 1072) 
3  The First Affiliated Hospital of Bengbu Medical College, Department of Hepatobiliary Surgery, Bengbu, People’s Republic of China (GRID:grid.414884.5) 
4  Anhui University of Technology, Department of Interventional, Affiliated Oriental Hospital, Huainan, People’s Republic of China (GRID:grid.440650.3) (ISNI:0000 0004 1790 1075) 
5  Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second Hospital, Huai’an, People’s Republic of China (GRID:grid.440648.a) 
6  Jinan University, Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Guangzhou, People’s Republic of China (GRID:grid.258164.c) (ISNI:0000 0004 1790 3548) 
Publication year
2020
Publication date
Dec 2020
Publisher
Springer Nature B.V.
ISSN
19317573
e-ISSN
1556276X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s11671-020-3289-z
ProQuest document ID
2383328262
Copyright
Nanoscale Research Letters is a copyright of Springer, (2020). All Rights Reserved. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.