Cargando…
pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation
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 synthesiz...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125917/ https://www.ncbi.nlm.nih.gov/pubmed/34066882 http://dx.doi.org/10.3390/polym13091515 |
_version_ | 1783693640678244352 |
---|---|
author | Xue, Xiukun Wu, Yanjuan Xu, Xiao Xu, Ben Chen, Zhaowei Li, Tianduo |
author_facet | Xue, Xiukun Wu, Yanjuan Xu, Xiao Xu, Ben Chen, Zhaowei Li, Tianduo |
author_sort | Xue, Xiukun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8125917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81259172021-05-17 pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation Xue, Xiukun Wu, Yanjuan Xu, Xiao Xu, Ben Chen, Zhaowei Li, Tianduo Polymers (Basel) Article 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. MDPI 2021-05-08 /pmc/articles/PMC8125917/ /pubmed/34066882 http://dx.doi.org/10.3390/polym13091515 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xue, Xiukun Wu, Yanjuan Xu, Xiao Xu, Ben Chen, Zhaowei Li, Tianduo pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation |
title | pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation |
title_full | pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation |
title_fullStr | pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation |
title_full_unstemmed | pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation |
title_short | pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation |
title_sort | ph and reduction dual-responsive bi-drugs conjugated dextran assemblies for combination chemotherapy and in vitro evaluation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125917/ https://www.ncbi.nlm.nih.gov/pubmed/34066882 http://dx.doi.org/10.3390/polym13091515 |
work_keys_str_mv | AT xuexiukun phandreductiondualresponsivebidrugsconjugateddextranassembliesforcombinationchemotherapyandinvitroevaluation AT wuyanjuan phandreductiondualresponsivebidrugsconjugateddextranassembliesforcombinationchemotherapyandinvitroevaluation AT xuxiao phandreductiondualresponsivebidrugsconjugateddextranassembliesforcombinationchemotherapyandinvitroevaluation AT xuben phandreductiondualresponsivebidrugsconjugateddextranassembliesforcombinationchemotherapyandinvitroevaluation AT chenzhaowei phandreductiondualresponsivebidrugsconjugateddextranassembliesforcombinationchemotherapyandinvitroevaluation AT litianduo phandreductiondualresponsivebidrugsconjugateddextranassembliesforcombinationchemotherapyandinvitroevaluation |