RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway

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 rad...

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Published inNanoscale 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
LanguageEnglish
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
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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
AbstractList 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.
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
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
ArticleNumber 63
Author Xu, Ruyue
Ma, Dong
Tang, Xiaolong
Xie, Yinghai
Zhou, Shuping
Huang, Xudong
Cai, Shuyu
Cao, Weiya
Zhang, Yinci
Liu, Xueke
Huo, Zhen
Xie, Chunmei
Shen, Jing
Liang, Yong
Wu, Binquan
Ma, Yongfang
Li, Amin
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Keywords Nanoparticles
Dactolisib (BEZ235)
Hepatocellular carcinoma
HIF-1α
Radiosensitivity
Language English
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DL Ou (3289_CR27) 2014; 13
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A Sathe (3289_CR26) 2018; 13
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R Marcos-Gragera (3289_CR23) 2012; 14
B Hong (3289_CR30) 2017; 8
N Golob-Schwarzl (3289_CR6) 2017; 83
YC Zhang (3289_CR7) 2019; 11
MM Kirstein (3289_CR13) 2013; 33
XL Tang (3289_CR16) 2018; 14
Z Bakhtiary (3289_CR19) 2016; 12
DW Kurniawan (3289_CR17) 2018; 288
CP Cui (3289_CR10) 2017; 66
H Gan (3289_CR14) 2018; 91
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SSID ssj0047076
Score 2.2885656
Snippet Polymer materials encapsulating drugs have broad prospects for drug delivery. We evaluated the effectiveness of polyethylene glycol-poly (lactic-co-glycolic...
Abstract Polymer materials encapsulating drugs have broad prospects for drug delivery. We evaluated the effectiveness of polyethylene glycol-poly...
SourceID pubmedcentral
proquest
crossref
springer
SourceType Open Access Repository
Aggregation Database
Publisher
SubjectTerms Biological effects
Chemistry and Materials Science
Materials Science
Molecular Medicine
Nano Express
Nanochemistry
Nanoscale Science and Technology
Nanotechnology
Nanotechnology and Microengineering
Polymers
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Title RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway
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https://pubmed.ncbi.nlm.nih.gov/PMC7099126
Volume 15
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