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Article

pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation

1
Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Science), Jinan 250353, China
2
Institute of Food Safety and Environment Monitoring, College of Chemistry, Fuzhou University, Fuzhou 350108, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Luis García-Fernández
Polymers 2021, 13(9), 1515; https://doi.org/10.3390/polym13091515
Received: 22 March 2021 / Revised: 21 April 2021 / Accepted: 28 April 2021 / Published: 8 May 2021
(This article belongs to the Special Issue Advanced Polymers for Biomedical Applications)
Polymeric prodrugs, synthesized by conjugating chemotherapeutic agents to functional polymers, have been extensively investigated and employed for safer and more efficacious cancer therapy. By rational design, a pH and reduction dual-sensitive dextran-di-drugs conjugate (oDex-g-Pt+DOX) was synthesized by the covalent conjugation of Pt (IV) prodrug and doxorubicin (DOX) to an oxidized dextran (oDex). Pt (IV) prodrug and DOX were linked by the versatile efficient esterification reactions and Schiff base reaction, respectively. oDex-g-Pt+DOX could self-assemble into nanoparticles with an average diameter at around 180 nm. The acidic and reductive (GSH) environment induced degradation and drug release behavior of the resulting nanoparticles (oDex-g-Pt+DOX NPs) were systematically investigated by optical experiment, DLS analysis, TEM measurement, and in vitro drugs release experiment. Effective cellular uptake of the oDex-g-Pt+DOX NPs was identified by the human cervical carcinoma HeLa cells via confocal laser scanning microscopy. Furthermore, oDex-g-Pt+DOX NPs displayed a comparable antiproliferative activity than the simple combination of free cisplatin and DOX (Cis+DOX) as the extension of time. More importantly, oDex-g-Pt+DOX NPs exhibited remarkable reversal ability of tumor resistance compared to the cisplatin in cisplatin-resistant lung carcinoma A549 cells. Take advantage of the acidic and reductive microenvironment of tumors, this smart polymer-dual-drugs conjugate could serve as a promising and effective nanomedicine for combination chemotherapy. View Full-Text
Keywords: polymeric prodrug; dual-sensitive; combination chemotherapy; drug conjugation; dextran polymeric prodrug; dual-sensitive; combination chemotherapy; drug conjugation; dextran
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MDPI and ACS Style

Xue, X.; Wu, Y.; Xu, X.; Xu, B.; Chen, Z.; Li, T. pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation. Polymers 2021, 13, 1515. https://doi.org/10.3390/polym13091515

AMA Style

Xue X, Wu Y, Xu X, Xu B, Chen Z, Li T. pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation. Polymers. 2021; 13(9):1515. https://doi.org/10.3390/polym13091515

Chicago/Turabian Style

Xue, Xiukun, Yanjuan Wu, Xiao Xu, Ben Xu, Zhaowei Chen, and Tianduo Li. 2021. "pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation" Polymers 13, no. 9: 1515. https://doi.org/10.3390/polym13091515

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