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MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy

Promoting tumor angiogenesis effectively and specifically to resolve tumor‐associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC‐T‐DOX, is constructed, that carries appropriately low‐density cilengitide, an αvβ3 integrin...

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Autores principales: Wei, Yan, Song, Sha, Duan, Nianxiu, Wang, Feng, Wang, Yuxi, Yang, Yiwei, Peng, Chengyuan, Li, Junjun, Nie, Di, Zhang, Xinxin, Guo, Shiyan, Zhu, Chunliu, Yu, Miaorong, Gan, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507343/
https://www.ncbi.nlm.nih.gov/pubmed/32995113
http://dx.doi.org/10.1002/advs.201902746
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author Wei, Yan
Song, Sha
Duan, Nianxiu
Wang, Feng
Wang, Yuxi
Yang, Yiwei
Peng, Chengyuan
Li, Junjun
Nie, Di
Zhang, Xinxin
Guo, Shiyan
Zhu, Chunliu
Yu, Miaorong
Gan, Yong
author_facet Wei, Yan
Song, Sha
Duan, Nianxiu
Wang, Feng
Wang, Yuxi
Yang, Yiwei
Peng, Chengyuan
Li, Junjun
Nie, Di
Zhang, Xinxin
Guo, Shiyan
Zhu, Chunliu
Yu, Miaorong
Gan, Yong
author_sort Wei, Yan
collection PubMed
description Promoting tumor angiogenesis effectively and specifically to resolve tumor‐associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC‐T‐DOX, is constructed, that carries appropriately low‐density cilengitide, an αvβ3 integrin‐specific Arg‐Gly‐Asp (RGD)‐mimetic cyclic peptide, via a membrane type 1‐matrix metalloproteinase (MT1‐MMP) cleavable peptide. After being administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, the proangiogenic activity of MC‐T‐DOX is specifically “turned on” in tumor vessels through cleavage by MT1‐MMP on tumor endothelial cells to release cilengitide. This locally released cilengitide increases tumor blood perfusion, thereby improving the accumulation and distribution of MC‐T‐DOX in the tumor site. The loaded‐DOX then displays enhanced penetration and increased cellular uptake upon heat‐triggered release from MC‐T‐DOX in the tumor interstitium, contributing to the improved tumor therapy efficacy. Therefore, the strategy of combining the modulation of tumor vascular promotion with smart nanodrug delivery represents a promising approach to improving drug delivery and therapeutic efficacy in a wide range of hypoperfused tumors.
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spelling pubmed-75073432020-09-28 MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy Wei, Yan Song, Sha Duan, Nianxiu Wang, Feng Wang, Yuxi Yang, Yiwei Peng, Chengyuan Li, Junjun Nie, Di Zhang, Xinxin Guo, Shiyan Zhu, Chunliu Yu, Miaorong Gan, Yong Adv Sci (Weinh) Full Papers Promoting tumor angiogenesis effectively and specifically to resolve tumor‐associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC‐T‐DOX, is constructed, that carries appropriately low‐density cilengitide, an αvβ3 integrin‐specific Arg‐Gly‐Asp (RGD)‐mimetic cyclic peptide, via a membrane type 1‐matrix metalloproteinase (MT1‐MMP) cleavable peptide. After being administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, the proangiogenic activity of MC‐T‐DOX is specifically “turned on” in tumor vessels through cleavage by MT1‐MMP on tumor endothelial cells to release cilengitide. This locally released cilengitide increases tumor blood perfusion, thereby improving the accumulation and distribution of MC‐T‐DOX in the tumor site. The loaded‐DOX then displays enhanced penetration and increased cellular uptake upon heat‐triggered release from MC‐T‐DOX in the tumor interstitium, contributing to the improved tumor therapy efficacy. Therefore, the strategy of combining the modulation of tumor vascular promotion with smart nanodrug delivery represents a promising approach to improving drug delivery and therapeutic efficacy in a wide range of hypoperfused tumors. John Wiley and Sons Inc. 2020-07-10 /pmc/articles/PMC7507343/ /pubmed/32995113 http://dx.doi.org/10.1002/advs.201902746 Text en © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Wei, Yan
Song, Sha
Duan, Nianxiu
Wang, Feng
Wang, Yuxi
Yang, Yiwei
Peng, Chengyuan
Li, Junjun
Nie, Di
Zhang, Xinxin
Guo, Shiyan
Zhu, Chunliu
Yu, Miaorong
Gan, Yong
MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
title MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
title_full MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
title_fullStr MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
title_full_unstemmed MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
title_short MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
title_sort mt1‐mmp‐activated liposomes to improve tumor blood perfusion and drug delivery for enhanced pancreatic cancer therapy
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507343/
https://www.ncbi.nlm.nih.gov/pubmed/32995113
http://dx.doi.org/10.1002/advs.201902746
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