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Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism
Background: As a classical autophagy inhibitor, CQ has been supposed to increase the sensitivity of tumors to chemotherapeutics. However, there exists a quite huge gap between laboratory research and clinical application, which is related to the distinct pharmacokinetic behavior of CQ to a great ext...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131275/ https://www.ncbi.nlm.nih.gov/pubmed/35664062 http://dx.doi.org/10.7150/thno.70852 |
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author | Wang, Juan Qiu, Liyan |
author_facet | Wang, Juan Qiu, Liyan |
author_sort | Wang, Juan |
collection | PubMed |
description | Background: As a classical autophagy inhibitor, CQ has been supposed to increase the sensitivity of tumors to chemotherapeutics. However, there exists a quite huge gap between laboratory research and clinical application, which is related to the distinct pharmacokinetic behavior of CQ to a great extent. Methods: Based on amphiphilic copolymer PPAP, a pH-responsive drug-induced self-assembled nanovesicle, named DC-DIV/C, was constructed to load DOX⋅HCl and CQ. The physicochemical properties of DC-DIV/C were characterized. To validate the cooperative action and delivery synchronism of DOX⋅HCl and CQ, cytotoxicity, apoptosis, cellular uptake and autophagy assay were investigated in DOX⋅HCl resistant cancer cells. The pharmacokinetic character and antitumor effect of DC-DIV/C were evaluated on rats and nude mice bearing xenograft drug-resistant K562/ADR tumors, respectively. Results: DC-DIV/C could simultaneously encapsulate DOX·HCl and CQ at the optimal ratio of 1:2. In vitro and in vivo tests confirmed that DC-DIV/C acted as an excellent vehicle for the synchronous delivery of DOX⋅HCl and CQ during the process of blood circulation, cellular uptake and intracellular release. Furthermore, CQ accomplished autophagy inhibition to reduce the IC(50) of DOX⋅HCl resistant cancer cells. Consequently, DC-DIV/C exhibited the extremely improved anti-tumor effect with 84.52% TIR on K562/ADR tumor. Conclusion: This study provides a promising and powerful strategy to achieve enhanced treatment outcomes for the precise combination therapy. |
format | Online Article Text |
id | pubmed-9131275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-91312752022-06-04 Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism Wang, Juan Qiu, Liyan Theranostics Research Paper Background: As a classical autophagy inhibitor, CQ has been supposed to increase the sensitivity of tumors to chemotherapeutics. However, there exists a quite huge gap between laboratory research and clinical application, which is related to the distinct pharmacokinetic behavior of CQ to a great extent. Methods: Based on amphiphilic copolymer PPAP, a pH-responsive drug-induced self-assembled nanovesicle, named DC-DIV/C, was constructed to load DOX⋅HCl and CQ. The physicochemical properties of DC-DIV/C were characterized. To validate the cooperative action and delivery synchronism of DOX⋅HCl and CQ, cytotoxicity, apoptosis, cellular uptake and autophagy assay were investigated in DOX⋅HCl resistant cancer cells. The pharmacokinetic character and antitumor effect of DC-DIV/C were evaluated on rats and nude mice bearing xenograft drug-resistant K562/ADR tumors, respectively. Results: DC-DIV/C could simultaneously encapsulate DOX·HCl and CQ at the optimal ratio of 1:2. In vitro and in vivo tests confirmed that DC-DIV/C acted as an excellent vehicle for the synchronous delivery of DOX⋅HCl and CQ during the process of blood circulation, cellular uptake and intracellular release. Furthermore, CQ accomplished autophagy inhibition to reduce the IC(50) of DOX⋅HCl resistant cancer cells. Consequently, DC-DIV/C exhibited the extremely improved anti-tumor effect with 84.52% TIR on K562/ADR tumor. Conclusion: This study provides a promising and powerful strategy to achieve enhanced treatment outcomes for the precise combination therapy. Ivyspring International Publisher 2022-05-13 /pmc/articles/PMC9131275/ /pubmed/35664062 http://dx.doi.org/10.7150/thno.70852 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wang, Juan Qiu, Liyan Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
title | Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
title_full | Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
title_fullStr | Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
title_full_unstemmed | Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
title_short | Drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
title_sort | drug-induced self-assembled nanovesicles for doxorubicin resistance reversal via autophagy inhibition and delivery synchronism |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131275/ https://www.ncbi.nlm.nih.gov/pubmed/35664062 http://dx.doi.org/10.7150/thno.70852 |
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