Cargando…

Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer

Application of drug combinations is a powerful strategy for the therapy of advanced gastric cancer. However, the clinical use of such combinations is greatly limited by the occurrence of severe systemic toxicity. Although polymeric-prodrug-based nanococktails can significantly reduce toxicity of dru...

Descripción completa

Detalles Bibliográficos
Autores principales: Pang, Lijun, Zhang, Lei, Zhou, Hong, Cao, Ling, Shao, Yueqin, Li, Tengyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931329/
https://www.ncbi.nlm.nih.gov/pubmed/35308794
http://dx.doi.org/10.3389/fchem.2022.844426
_version_ 1784671234829582336
author Pang, Lijun
Zhang, Lei
Zhou, Hong
Cao, Ling
Shao, Yueqin
Li, Tengyun
author_facet Pang, Lijun
Zhang, Lei
Zhou, Hong
Cao, Ling
Shao, Yueqin
Li, Tengyun
author_sort Pang, Lijun
collection PubMed
description Application of drug combinations is a powerful strategy for the therapy of advanced gastric cancer. However, the clinical use of such combinations is greatly limited by the occurrence of severe systemic toxicity. Although polymeric-prodrug-based nanococktails can significantly reduce toxicity of drugs, they have been shown to have low intracellular drug release. To balance between efficacy and safety during application of polymeric-prodrug-based nanococktails, a reactive oxygen species (ROS)-responsive nanococktail (PCM) with self-amplification drug release was developed in this study. In summary, PCM micelles were co-assembled from ROS-sensitive cucurbitacin B (CuB) and paclitaxel (PTX) polymeric prodrug, which were fabricated by covalently grafting PTX and CuB to dextran via an ROS-sensitive linkage. To minimize the side effects of the PCM micelles, a polymeric-prodrug strategy was employed to prevent premature leakage. Once it entered cancer cells, PCM released CuB and PTX in response to ROS. Moreover, the released CuB further promoted ROS generation, which in turn enhanced drug release for better therapeutic effects. In vivo antitumor experiments showed that the PCM-treated group had lower tumor burden (tumor weight was reduced by 92%), but bodyweight loss was not significant. These results indicate that the developed polymeric prodrug, with a self-amplification drug release nanococktail strategy, can be an effective and safe strategy for cancer management.
format Online
Article
Text
id pubmed-8931329
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89313292022-03-19 Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer Pang, Lijun Zhang, Lei Zhou, Hong Cao, Ling Shao, Yueqin Li, Tengyun Front Chem Chemistry Application of drug combinations is a powerful strategy for the therapy of advanced gastric cancer. However, the clinical use of such combinations is greatly limited by the occurrence of severe systemic toxicity. Although polymeric-prodrug-based nanococktails can significantly reduce toxicity of drugs, they have been shown to have low intracellular drug release. To balance between efficacy and safety during application of polymeric-prodrug-based nanococktails, a reactive oxygen species (ROS)-responsive nanococktail (PCM) with self-amplification drug release was developed in this study. In summary, PCM micelles were co-assembled from ROS-sensitive cucurbitacin B (CuB) and paclitaxel (PTX) polymeric prodrug, which were fabricated by covalently grafting PTX and CuB to dextran via an ROS-sensitive linkage. To minimize the side effects of the PCM micelles, a polymeric-prodrug strategy was employed to prevent premature leakage. Once it entered cancer cells, PCM released CuB and PTX in response to ROS. Moreover, the released CuB further promoted ROS generation, which in turn enhanced drug release for better therapeutic effects. In vivo antitumor experiments showed that the PCM-treated group had lower tumor burden (tumor weight was reduced by 92%), but bodyweight loss was not significant. These results indicate that the developed polymeric prodrug, with a self-amplification drug release nanococktail strategy, can be an effective and safe strategy for cancer management. Frontiers Media S.A. 2022-03-04 /pmc/articles/PMC8931329/ /pubmed/35308794 http://dx.doi.org/10.3389/fchem.2022.844426 Text en Copyright © 2022 Pang, Zhang, Zhou, Cao, Shao and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Pang, Lijun
Zhang, Lei
Zhou, Hong
Cao, Ling
Shao, Yueqin
Li, Tengyun
Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer
title Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer
title_full Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer
title_fullStr Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer
title_full_unstemmed Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer
title_short Reactive Oxygen Species-Responsive Nanococktail With Self-Amplificated Drug Release for Efficient Co-Delivery of Paclitaxel/Cucurbitacin B and Synergistic Treatment of Gastric Cancer
title_sort reactive oxygen species-responsive nanococktail with self-amplificated drug release for efficient co-delivery of paclitaxel/cucurbitacin b and synergistic treatment of gastric cancer
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931329/
https://www.ncbi.nlm.nih.gov/pubmed/35308794
http://dx.doi.org/10.3389/fchem.2022.844426
work_keys_str_mv AT panglijun reactiveoxygenspeciesresponsivenanococktailwithselfamplificateddrugreleaseforefficientcodeliveryofpaclitaxelcucurbitacinbandsynergistictreatmentofgastriccancer
AT zhanglei reactiveoxygenspeciesresponsivenanococktailwithselfamplificateddrugreleaseforefficientcodeliveryofpaclitaxelcucurbitacinbandsynergistictreatmentofgastriccancer
AT zhouhong reactiveoxygenspeciesresponsivenanococktailwithselfamplificateddrugreleaseforefficientcodeliveryofpaclitaxelcucurbitacinbandsynergistictreatmentofgastriccancer
AT caoling reactiveoxygenspeciesresponsivenanococktailwithselfamplificateddrugreleaseforefficientcodeliveryofpaclitaxelcucurbitacinbandsynergistictreatmentofgastriccancer
AT shaoyueqin reactiveoxygenspeciesresponsivenanococktailwithselfamplificateddrugreleaseforefficientcodeliveryofpaclitaxelcucurbitacinbandsynergistictreatmentofgastriccancer
AT litengyun reactiveoxygenspeciesresponsivenanococktailwithselfamplificateddrugreleaseforefficientcodeliveryofpaclitaxelcucurbitacinbandsynergistictreatmentofgastriccancer