Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer

Lian Deng,1,* Xiongjie Zhu,1,* Zhongjian Yu,1 Ying Li,1 Lingyu Qin,1 Zhile Liu,1 Longbao Feng,2 Rui Guo,2 Yanfang Zheng1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 2Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guang...

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Autores principales:	Deng L, Zhu X, Yu Z, Li Y, Qin L, Liu Z, Feng L, Guo R, Zheng Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	nanocarrier t7 peptide ph-responsive docetaxel esophageal cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1cfedbd72de94ac88ccac484e007bd9b
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spelling	oai:doaj.org-article:1cfedbd72de94ac88ccac484e007bd9b2021-12-02T11:12:17ZNovel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer1178-2013https://doaj.org/article/1cfedbd72de94ac88ccac484e007bd9b2020-10-01T00:00:00Zhttps://www.dovepress.com/novel-t7-modified-ph-responsive-targeted-nanosystem-for-co-delivery-of-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lian Deng,1,* Xiongjie Zhu,1,* Zhongjian Yu,1 Ying Li,1 Lingyu Qin,1 Zhile Liu,1 Longbao Feng,2 Rui Guo,2 Yanfang Zheng1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 2Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China*These authors contributed equally to this workCorrespondence: Yanfang Zheng; Rui Guo Tel +86 18665000236Email 18665000236@163.com; guorui@jnu.edu.cnBackground: Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods: Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results: T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion: The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.Keywords: nanocarrier, T7 peptide, pH-responsive, docetaxel, esophageal cancerDeng LZhu XYu ZLi YQin LLiu ZFeng LGuo RZheng YDove Medical Pressarticlenanocarriert7 peptideph-responsivedocetaxelesophageal cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 7745-7762 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanocarrier t7 peptide ph-responsive docetaxel esophageal cancer Medicine (General) R5-920
spellingShingle	nanocarrier t7 peptide ph-responsive docetaxel esophageal cancer Medicine (General) R5-920 Deng L Zhu X Yu Z Li Y Qin L Liu Z Feng L Guo R Zheng Y Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
description	Lian Deng,1,* Xiongjie Zhu,1,* Zhongjian Yu,1 Ying Li,1 Lingyu Qin,1 Zhile Liu,1 Longbao Feng,2 Rui Guo,2 Yanfang Zheng1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China; 2Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China*These authors contributed equally to this workCorrespondence: Yanfang Zheng; Rui Guo Tel +86 18665000236Email 18665000236@163.com; guorui@jnu.edu.cnBackground: Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods: Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results: T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion: The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.Keywords: nanocarrier, T7 peptide, pH-responsive, docetaxel, esophageal cancer
format	article
author	Deng L Zhu X Yu Z Li Y Qin L Liu Z Feng L Guo R Zheng Y
author_facet	Deng L Zhu X Yu Z Li Y Qin L Liu Z Feng L Guo R Zheng Y
author_sort	Deng L
title	Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
title_short	Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
title_full	Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
title_fullStr	Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
title_full_unstemmed	Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer
title_sort	novel t7-modified ph-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/1cfedbd72de94ac88ccac484e007bd9b
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Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer

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