Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

Ming Shao,1,* Weitao Zhu,2,* Xianping Lv,1 Qiankun Yang,1 Xin Liu,1 Ying Xie,1 Ping Tang,3 Ling Sun3 1Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China; 2Department of Clinical Laboratory, The First Affiliated Hospital of...

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Autores principales:	Shao M, Zhu WT, Lv XP, Yang QK, Liu X, Xie Y, Tang P, Sun L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	ovarian cancer chloroquine chemo-sensitizer MPEG-PLA nanoparticles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5e6c708505704e52bc51a7aec2a06b29
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spelling	oai:doaj.org-article:5e6c708505704e52bc51a7aec2a06b292021-12-02T05:47:03ZEncapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer1178-2013https://doaj.org/article/5e6c708505704e52bc51a7aec2a06b292018-12-01T00:00:00Zhttps://www.dovepress.com/encapsulation-of-chloroquine-and-doxorubicin-by-mpeg-pla-to-enhance-an-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ming Shao,1,* Weitao Zhu,2,* Xianping Lv,1 Qiankun Yang,1 Xin Liu,1 Ying Xie,1 Ping Tang,3 Ling Sun3 1Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China; 3Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China *These authors contributed equally to this work Purpose: As the deadliest gynecological malignancy, ovarian cancer ranks as a major cause of disease-related deaths to women worldwide and is treated with transurethral resection or systemic chemotherapy. However, traditional chemotherapeutic drug in antitumor therapy has shown unavoidable limitations, such as poor curative effects, systemic toxicity and development of drug resistance, leading to failure of tumor inhibition and recurrence. This study aims to explore an innovative method to enhance the clinical efficiency of ovarian cancer.Materials and methods: Using MTT assay, the cell viability was detected under different culture systems. Western blot was used to examine the expression of P-gp in doxorubicin-resistant and wild-type A2780/SKOV3 cells. We used confocal to examine the drug concentration under different culture conditions. Also, flow cytometry was used to detect the drug absorption at the determined time points under different culture systems. Using nude mice model, we evaluated the killing efficacy of chemotherapeutic drugs with or without nanoparticle encapsulation. ELISA was used to examine the levels of creatinine, alanine aminotransferase and aspartate aminotransferase in plasma.Results: We found that pretreatment of chloroquine (CQ) as chemosensitizer markedly enhanced the anticancer effects in ovarian cancer. We also provided evidence that CQ efficiently increase the pH value of lysosomes in tumor cells, leading to the reverse of drug sequestration induced by lysosomes. To further improve the pharmacokinetics profiles and avoid the systemic toxicity caused by chemotherapeutic agents, we encapsulated CQ and chemotherapeutic drugs by polymeric nanoparticles methoxy poly(ethylene glycol)-poly(L-lactic acid). Codelivery of CQ and chemotherapeutic agents by nanocarrier revealed enhanced anticancer effects compared with the free drug delivery by tail vein injection. More importantly, accumulated drugs, prolonged drug circulation and reduced organic damages were observed in nanoparticles delivery.Conclusion: Codelivery of CQ and chemotherapeutic drugs by methoxy poly(ethylene glycol)-poly(L-lactic acid) could significantly improve the anticancer effects and might have important potency in clinical applications for ovarian cancer therapy. Keywords: ovarian cancer, chloroquine, cisplatin, MPEG-PLA, nanoparticles Shao MZhu WTLv XPYang QKLiu XXie YTang PSun LDove Medical Pressarticleovarian cancerchloroquinechemo-sensitizerMPEG-PLAnanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8231-8245 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	ovarian cancer chloroquine chemo-sensitizer MPEG-PLA nanoparticles Medicine (General) R5-920
spellingShingle	ovarian cancer chloroquine chemo-sensitizer MPEG-PLA nanoparticles Medicine (General) R5-920 Shao M Zhu WT Lv XP Yang QK Liu X Xie Y Tang P Sun L Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer
description	Ming Shao,1,* Weitao Zhu,2,* Xianping Lv,1 Qiankun Yang,1 Xin Liu,1 Ying Xie,1 Ping Tang,3 Ling Sun3 1Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China; 3Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China *These authors contributed equally to this work Purpose: As the deadliest gynecological malignancy, ovarian cancer ranks as a major cause of disease-related deaths to women worldwide and is treated with transurethral resection or systemic chemotherapy. However, traditional chemotherapeutic drug in antitumor therapy has shown unavoidable limitations, such as poor curative effects, systemic toxicity and development of drug resistance, leading to failure of tumor inhibition and recurrence. This study aims to explore an innovative method to enhance the clinical efficiency of ovarian cancer.Materials and methods: Using MTT assay, the cell viability was detected under different culture systems. Western blot was used to examine the expression of P-gp in doxorubicin-resistant and wild-type A2780/SKOV3 cells. We used confocal to examine the drug concentration under different culture conditions. Also, flow cytometry was used to detect the drug absorption at the determined time points under different culture systems. Using nude mice model, we evaluated the killing efficacy of chemotherapeutic drugs with or without nanoparticle encapsulation. ELISA was used to examine the levels of creatinine, alanine aminotransferase and aspartate aminotransferase in plasma.Results: We found that pretreatment of chloroquine (CQ) as chemosensitizer markedly enhanced the anticancer effects in ovarian cancer. We also provided evidence that CQ efficiently increase the pH value of lysosomes in tumor cells, leading to the reverse of drug sequestration induced by lysosomes. To further improve the pharmacokinetics profiles and avoid the systemic toxicity caused by chemotherapeutic agents, we encapsulated CQ and chemotherapeutic drugs by polymeric nanoparticles methoxy poly(ethylene glycol)-poly(L-lactic acid). Codelivery of CQ and chemotherapeutic agents by nanocarrier revealed enhanced anticancer effects compared with the free drug delivery by tail vein injection. More importantly, accumulated drugs, prolonged drug circulation and reduced organic damages were observed in nanoparticles delivery.Conclusion: Codelivery of CQ and chemotherapeutic drugs by methoxy poly(ethylene glycol)-poly(L-lactic acid) could significantly improve the anticancer effects and might have important potency in clinical applications for ovarian cancer therapy. Keywords: ovarian cancer, chloroquine, cisplatin, MPEG-PLA, nanoparticles
format	article
author	Shao M Zhu WT Lv XP Yang QK Liu X Xie Y Tang P Sun L
author_facet	Shao M Zhu WT Lv XP Yang QK Liu X Xie Y Tang P Sun L
author_sort	Shao M
title	Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer
title_short	Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer
title_full	Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer
title_fullStr	Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer
title_full_unstemmed	Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer
title_sort	encapsulation of chloroquine and doxorubicin by mpeg-pla to enhance anticancer effects by lysosomes inhibition in ovarian cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/5e6c708505704e52bc51a7aec2a06b29
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Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

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