Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy

Yaqiao Li; Lingxiao Li; Qianhui Jin; Tian  Liu; Jin  Sun; Yongjun Wang; Zhijun  Yang; Zhonggui He; Bingjun Sun

doi:10.1016/j.ajps.2022.02.002

Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy

Yaqiao Li
, Lingxiao Li
, Qianhui Jin
, Tian Liu
, Jin Sun
, Yongjun Wang
, Zhijun Yang
, Zhonggui He^*
, Bingjun Sun^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

52 Citations (Scopus)

Abstract

PEGylation has been widely used to improve the pharmacokinetic properties of prodrug self-assembled nanoparticles (prodrug-SANPs). However, the impacts of the amount of PEG on the self-assemble stability, cellular uptake, pharmacokinetics, and antitumor efficacy of prodrug-SANPs are still unknown. Herein, selenoether bond bridged docetaxel dimeric prodrug was synthesized as the model prodrug. Five prodrug-SANPs were designed by using different mass ratios of prodrugs to PEG (W_prodrug/W_{DSPE-mPEG2000} = 10:0, 9:1, 8:2, 7:3 and 6:4), and defined as Pure drug NPs, 9:1NPs, 8:2NPs, 7:3 NPs and 6:4 NPs, respectively. Interestingly, 8:2 NPs formed the most compact nanostructure, thus improving the self-assemble stability and pharmacokinetics behavior. In addition, the difference of these prodrug-SANPs in cellular uptake was investigated, and the influence of PEG on cytotoxicity and antitumor efficacy was also clarified in details. The 8:2 NPs exhibited much better antitumor efficacy than other prodrug-SANPs and even commercial product. Our findings demonstrated the pivotal role of the amount of PEG on prodrug-SANPs.

Original language	English
Pages (from-to)	241-252
Number of pages	12
Journal	Asian Journal of Pharmaceutical Sciences
Volume	17
Issue number	2
DOIs	https://doi.org/10.1016/j.ajps.2022.02.002
Publication status	Published - Mar 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

User-Defined Keywords

Docetaxel
Oxidation responsive
PEGylation
Prodrug
Self-assembly nanoparticles

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10.1016/j.ajps.2022.02.002

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title = "Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy",

abstract = "PEGylation has been widely used to improve the pharmacokinetic properties of prodrug self-assembled nanoparticles (prodrug-SANPs). However, the impacts of the amount of PEG on the self-assemble stability, cellular uptake, pharmacokinetics, and antitumor efficacy of prodrug-SANPs are still unknown. Herein, selenoether bond bridged docetaxel dimeric prodrug was synthesized as the model prodrug. Five prodrug-SANPs were designed by using different mass ratios of prodrugs to PEG (Wprodrug/WDSPE-mPEG2000 = 10:0, 9:1, 8:2, 7:3 and 6:4), and defined as Pure drug NPs, 9:1NPs, 8:2NPs, 7:3 NPs and 6:4 NPs, respectively. Interestingly, 8:2 NPs formed the most compact nanostructure, thus improving the self-assemble stability and pharmacokinetics behavior. In addition, the difference of these prodrug-SANPs in cellular uptake was investigated, and the influence of PEG on cytotoxicity and antitumor efficacy was also clarified in details. The 8:2 NPs exhibited much better antitumor efficacy than other prodrug-SANPs and even commercial product. Our findings demonstrated the pivotal role of the amount of PEG on prodrug-SANPs.",

keywords = "Docetaxel, Oxidation responsive, PEGylation, Prodrug, Self-assembly nanoparticles",

author = "Yaqiao Li and Lingxiao Li and Qianhui Jin and Tian Liu and Jin Sun and Yongjun Wang and Zhijun Yang and Zhonggui He and Bingjun Sun",

note = "Funding Information: This work was financially supported by National Natural Science Foundation of China (no. 81872816), Doctoral Scientific Research Staring Foundation of Liaoning Province (no. 2021-BS-130), General Program of Department of Education of Liaoning Province (no. LJKZ0953). Publisher Copyright: {\textcopyright} 2022 Shenyang Pharmaceutical University. Published by Elsevier B.V. ",

year = "2022",

month = mar,

doi = "10.1016/j.ajps.2022.02.002",

language = "English",

volume = "17",

pages = "241--252",

journal = "Asian Journal of Pharmaceutical Sciences",

issn = "1818-0876",

publisher = "Shenyang Pharmaceutical University",

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}

TY - JOUR

T1 - Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy

AU - Li, Yaqiao

AU - Li, Lingxiao

AU - Jin, Qianhui

AU - Liu, Tian

AU - Sun, Jin

AU - Wang, Yongjun

AU - Yang, Zhijun

AU - He, Zhonggui

AU - Sun, Bingjun

N1 - Funding Information: This work was financially supported by National Natural Science Foundation of China (no. 81872816), Doctoral Scientific Research Staring Foundation of Liaoning Province (no. 2021-BS-130), General Program of Department of Education of Liaoning Province (no. LJKZ0953). Publisher Copyright: © 2022 Shenyang Pharmaceutical University. Published by Elsevier B.V.

PY - 2022/3

Y1 - 2022/3

N2 - PEGylation has been widely used to improve the pharmacokinetic properties of prodrug self-assembled nanoparticles (prodrug-SANPs). However, the impacts of the amount of PEG on the self-assemble stability, cellular uptake, pharmacokinetics, and antitumor efficacy of prodrug-SANPs are still unknown. Herein, selenoether bond bridged docetaxel dimeric prodrug was synthesized as the model prodrug. Five prodrug-SANPs were designed by using different mass ratios of prodrugs to PEG (Wprodrug/WDSPE-mPEG2000 = 10:0, 9:1, 8:2, 7:3 and 6:4), and defined as Pure drug NPs, 9:1NPs, 8:2NPs, 7:3 NPs and 6:4 NPs, respectively. Interestingly, 8:2 NPs formed the most compact nanostructure, thus improving the self-assemble stability and pharmacokinetics behavior. In addition, the difference of these prodrug-SANPs in cellular uptake was investigated, and the influence of PEG on cytotoxicity and antitumor efficacy was also clarified in details. The 8:2 NPs exhibited much better antitumor efficacy than other prodrug-SANPs and even commercial product. Our findings demonstrated the pivotal role of the amount of PEG on prodrug-SANPs.

AB - PEGylation has been widely used to improve the pharmacokinetic properties of prodrug self-assembled nanoparticles (prodrug-SANPs). However, the impacts of the amount of PEG on the self-assemble stability, cellular uptake, pharmacokinetics, and antitumor efficacy of prodrug-SANPs are still unknown. Herein, selenoether bond bridged docetaxel dimeric prodrug was synthesized as the model prodrug. Five prodrug-SANPs were designed by using different mass ratios of prodrugs to PEG (Wprodrug/WDSPE-mPEG2000 = 10:0, 9:1, 8:2, 7:3 and 6:4), and defined as Pure drug NPs, 9:1NPs, 8:2NPs, 7:3 NPs and 6:4 NPs, respectively. Interestingly, 8:2 NPs formed the most compact nanostructure, thus improving the self-assemble stability and pharmacokinetics behavior. In addition, the difference of these prodrug-SANPs in cellular uptake was investigated, and the influence of PEG on cytotoxicity and antitumor efficacy was also clarified in details. The 8:2 NPs exhibited much better antitumor efficacy than other prodrug-SANPs and even commercial product. Our findings demonstrated the pivotal role of the amount of PEG on prodrug-SANPs.

KW - Docetaxel

KW - Oxidation responsive

KW - PEGylation

KW - Prodrug

KW - Self-assembly nanoparticles

UR - https://www.scopus.com/pages/publications/85127596005

U2 - 10.1016/j.ajps.2022.02.002

DO - 10.1016/j.ajps.2022.02.002

M3 - Journal article

AN - SCOPUS:85127596005

SN - 1818-0876

VL - 17

SP - 241

EP - 252

JO - Asian Journal of Pharmaceutical Sciences

JF - Asian Journal of Pharmaceutical Sciences

IS - 2

ER -

Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy

Abstract

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