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 - http://www.scopus.com/inward/record.url?scp=85127596005&partnerID=8YFLogxK
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 -