Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells

Abstract Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for ind...

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Autores principales:	Akram Rahmani, Fariborz Rahimi, Mehrdad Iranshahi, Houman Kahroba, Amir Zarebkohan, Mehdi Talebi, Roya Salehi, Hassan Zavvar Mousavi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ae2574e1aa34cacb415e88f73f4b570
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spelling	oai:doaj.org-article:2ae2574e1aa34cacb415e88f73f4b5702021-11-08T10:53:40ZCo-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells10.1038/s41598-021-00954-82045-2322https://doaj.org/article/2ae2574e1aa34cacb415e88f73f4b5702021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00954-8https://doaj.org/toc/2045-2322Abstract Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for inducing apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process. Micelles obtained from the novel copolymer showed exceptional properties such as small size of around 34.5 nm, CMC of 0.1 μg/mL, and cell internalization of around 100% at 30 min. These novel engineered micelles were used for combination delivery of doxorubicin-conferone with high encapsulation efficiency of near 100% for both drugs. Our results show that combination delivery of Dox and Conf to MDA-MB-231 cells had synergistic effects (CI < 1). According to cell cycle and Annexin-V apoptosis analysis, Dox-Conf loaded micelle significantly induce tumor cell apoptosis (more than 98% of cells population showed apoptosis at IC 50 = 0.259 μg/mL). RT-PCR and western-blot tests show that Dox-Conf loaded βCD-g-PMA-co-PLGA micelle induced apoptosis via intrinsic pathway. Therefore, the unique design of multi-functional pH-sensitive micelles open a new perspective for the development of nanomedicine for combination chemo-adjuvant therapy against malignant cancer.Akram RahmaniFariborz RahimiMehrdad IranshahiHouman KahrobaAmir ZarebkohanMehdi TalebiRoya SalehiHassan Zavvar MousaviNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akram Rahmani Fariborz Rahimi Mehrdad Iranshahi Houman Kahroba Amir Zarebkohan Mehdi Talebi Roya Salehi Hassan Zavvar Mousavi Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
description	Abstract Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for inducing apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process. Micelles obtained from the novel copolymer showed exceptional properties such as small size of around 34.5 nm, CMC of 0.1 μg/mL, and cell internalization of around 100% at 30 min. These novel engineered micelles were used for combination delivery of doxorubicin-conferone with high encapsulation efficiency of near 100% for both drugs. Our results show that combination delivery of Dox and Conf to MDA-MB-231 cells had synergistic effects (CI < 1). According to cell cycle and Annexin-V apoptosis analysis, Dox-Conf loaded micelle significantly induce tumor cell apoptosis (more than 98% of cells population showed apoptosis at IC 50 = 0.259 μg/mL). RT-PCR and western-blot tests show that Dox-Conf loaded βCD-g-PMA-co-PLGA micelle induced apoptosis via intrinsic pathway. Therefore, the unique design of multi-functional pH-sensitive micelles open a new perspective for the development of nanomedicine for combination chemo-adjuvant therapy against malignant cancer.
format	article
author	Akram Rahmani Fariborz Rahimi Mehrdad Iranshahi Houman Kahroba Amir Zarebkohan Mehdi Talebi Roya Salehi Hassan Zavvar Mousavi
author_facet	Akram Rahmani Fariborz Rahimi Mehrdad Iranshahi Houman Kahroba Amir Zarebkohan Mehdi Talebi Roya Salehi Hassan Zavvar Mousavi
author_sort	Akram Rahmani
title	Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
title_short	Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
title_full	Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
title_fullStr	Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
title_full_unstemmed	Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
title_sort	co-delivery of doxorubicin and conferone by novel ph-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2ae2574e1aa34cacb415e88f73f4b570
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Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells

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