Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy

Qing Hu,1,2,* Yifei Wang,1,* Lu Xu,1,* Dawei Chen,1,3 Lifang Cheng1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China; 2Department of Pharmaceutics, College of Pharmaceutical Sciences, Fujian Medical University,...

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Autores principales:	Hu Q, Wang Y, Xu L, Chen D, Cheng L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	poly(amidoamine) dendrimers histidine transferrin doxorubicin ph and redox-sensitivity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1582a7f1dd62467589a6a84448452b04
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spelling	oai:doaj.org-article:1582a7f1dd62467589a6a84448452b042021-12-02T09:18:06ZTransferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy1178-2013https://doaj.org/article/1582a7f1dd62467589a6a84448452b042020-04-01T00:00:00Zhttps://www.dovepress.com/transferrin-conjugated-ph--and-redox-responsive-polyamidoamine-dendrim-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Qing Hu,1,2,* Yifei Wang,1,* Lu Xu,1,* Dawei Chen,1,3 Lifang Cheng1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China; 2Department of Pharmaceutics, College of Pharmaceutical Sciences, Fujian Medical University, Fuzhou 350122, People’s Republic of China; 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifang Cheng Email chenglifang0803@126.comIntroduction: A multifunctional redox- and pH-responsive polymeric drug delivery system is designed and investigated for targeted anticancer drug delivery to liver cancer.Methods: The nanocarrier (His-PAMAM-ss-PEG-Tf, HP-ss-PEG-Tf) is constructed based on generation 4 polyamidoamine dendrimer (G4 PAMAM). Optimized amount of histidine (His) residues is grafted on the surface of PAMAM to obtain enhanced pH-sensitivity and proton-buffering capacity. Disulfide bonds (ss) are introduced between PAMAM and PEG to reach accelerated intracellular drug release. Transferrin (Tf) was applied to achieve active tumor targeting. Doxorubicin (DOX) is loaded in the hydrophobic cavity of the nanocarrier to exert its anti-tumor effect.Results: The results obtained from in vitro and in vivo evaluation indicate that HP-ss-PEG-Tf/DOX complex has pH and redox dual-sensitive properties, and exhibit higher cellular uptake and cytotoxicity than the other control groups. Flow cytometry and confocal microscopy display internalization of HP-ss-PEG-Tf/DOX via clathrin mediated endocytosis and effective endosomal escape in HepG2 cancer cells. Additionally, cyanine 7 labeled HP-ss-PEG-Tf conjugate could quickly accumulate in the HepG2 tumor. Remarkably, HP-ss-PEG-Tf/DOX present superior anticancer activity, enhanced apoptotic activity and lower heart and kidney toxicity in vivo.Discussion: Thus, HP-ss-PEG-Tf is proved to be a promising candidate for effective targeting delivery of DOX into the tumor.Keywords: poly(amidoamine) dendrimers, histidine, transferrin, doxorubicin, pH and redox sensitivityHu QWang YXu LChen DCheng LDove Medical Pressarticlepoly(amidoamine) dendrimershistidinetransferrindoxorubicinph and redox-sensitivityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2751-2764 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	poly(amidoamine) dendrimers histidine transferrin doxorubicin ph and redox-sensitivity Medicine (General) R5-920
spellingShingle	poly(amidoamine) dendrimers histidine transferrin doxorubicin ph and redox-sensitivity Medicine (General) R5-920 Hu Q Wang Y Xu L Chen D Cheng L Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy
description	Qing Hu,1,2,* Yifei Wang,1,* Lu Xu,1,* Dawei Chen,1,3 Lifang Cheng1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China; 2Department of Pharmaceutics, College of Pharmaceutical Sciences, Fujian Medical University, Fuzhou 350122, People’s Republic of China; 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifang Cheng Email chenglifang0803@126.comIntroduction: A multifunctional redox- and pH-responsive polymeric drug delivery system is designed and investigated for targeted anticancer drug delivery to liver cancer.Methods: The nanocarrier (His-PAMAM-ss-PEG-Tf, HP-ss-PEG-Tf) is constructed based on generation 4 polyamidoamine dendrimer (G4 PAMAM). Optimized amount of histidine (His) residues is grafted on the surface of PAMAM to obtain enhanced pH-sensitivity and proton-buffering capacity. Disulfide bonds (ss) are introduced between PAMAM and PEG to reach accelerated intracellular drug release. Transferrin (Tf) was applied to achieve active tumor targeting. Doxorubicin (DOX) is loaded in the hydrophobic cavity of the nanocarrier to exert its anti-tumor effect.Results: The results obtained from in vitro and in vivo evaluation indicate that HP-ss-PEG-Tf/DOX complex has pH and redox dual-sensitive properties, and exhibit higher cellular uptake and cytotoxicity than the other control groups. Flow cytometry and confocal microscopy display internalization of HP-ss-PEG-Tf/DOX via clathrin mediated endocytosis and effective endosomal escape in HepG2 cancer cells. Additionally, cyanine 7 labeled HP-ss-PEG-Tf conjugate could quickly accumulate in the HepG2 tumor. Remarkably, HP-ss-PEG-Tf/DOX present superior anticancer activity, enhanced apoptotic activity and lower heart and kidney toxicity in vivo.Discussion: Thus, HP-ss-PEG-Tf is proved to be a promising candidate for effective targeting delivery of DOX into the tumor.Keywords: poly(amidoamine) dendrimers, histidine, transferrin, doxorubicin, pH and redox sensitivity
format	article
author	Hu Q Wang Y Xu L Chen D Cheng L
author_facet	Hu Q Wang Y Xu L Chen D Cheng L
author_sort	Hu Q
title	Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy
title_short	Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy
title_full	Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy
title_fullStr	Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy
title_full_unstemmed	Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy
title_sort	transferrin conjugated ph- and redox-responsive poly(amidoamine) dendrimer conjugate as an efficient drug delivery carrier for cancer therapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/1582a7f1dd62467589a6a84448452b04
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Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy

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