ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication

Although podophyllotoxin (POD) demonstrates high efficiency to inhibit various cancers, its clinic application is limited to poor bioavailability. Nanoparticles derived from homodimeric prodrugs with high drug loading potential are emerging as promising nanomedicines. However, complete intracellular...

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Autores principales:	Bingfeng Liang, Dangxia Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	dimeric prodrug ros generation vitamin k3 high drug loading tumor-specific drug release Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/da7bb055d1f84c14ade51f33adb8afb5
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spelling	oai:doaj.org-article:da7bb055d1f84c14ade51f33adb8afb52021-11-11T14:23:41ZROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication1071-75441521-046410.1080/10717544.2021.1995076https://doaj.org/article/da7bb055d1f84c14ade51f33adb8afb52021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.1995076https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464Although podophyllotoxin (POD) demonstrates high efficiency to inhibit various cancers, its clinic application is limited to poor bioavailability. Nanoparticles derived from homodimeric prodrugs with high drug loading potential are emerging as promising nanomedicines. However, complete intracellular drug release remains a major hindrance to the use of homodimeric prodrugs-based nanomedicine. We sought to develop a reactive oxygen species (ROS) responsive POD dimeric prodrug by incorporating vitamin K3 (VK3) and Pluronic F127 to synthesize a spheroid nanoparticle (PTV-NPs). PTV-NPs with high POD content could release drugs under the ROS enrichment microenvironment in cancer cells. The released VK3 could produce abundant ROS selectively in tumor cells catalyzed by the overexpressed NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme. In turn, the resultant high ROS concentration promoted the conversion of POD dimeric prodrug to POD monomer, thereby achieving the selective killing of cancer cells with weak system toxicity. In vitro and in vivo studies consistently confirmed that PTV-NPs exhibit high drug loading potential and upstanding bioavailability. They are also effectively internalized by tumor cells, induce abundant intracellular ROS generation, and have high tumor-specific cytotoxicity. This ROS-responsive dimeric prodrug nanoplatform characterized by selective self-amplification drug release may hold promise in the field of antitumor drug delivery.Bingfeng LiangDangxia ZhouTaylor & Francis Grouparticledimeric prodrugros generationvitamin k3high drug loadingtumor-specific drug releaseTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2361-2372 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dimeric prodrug ros generation vitamin k3 high drug loading tumor-specific drug release Therapeutics. Pharmacology RM1-950
spellingShingle	dimeric prodrug ros generation vitamin k3 high drug loading tumor-specific drug release Therapeutics. Pharmacology RM1-950 Bingfeng Liang Dangxia Zhou ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
description	Although podophyllotoxin (POD) demonstrates high efficiency to inhibit various cancers, its clinic application is limited to poor bioavailability. Nanoparticles derived from homodimeric prodrugs with high drug loading potential are emerging as promising nanomedicines. However, complete intracellular drug release remains a major hindrance to the use of homodimeric prodrugs-based nanomedicine. We sought to develop a reactive oxygen species (ROS) responsive POD dimeric prodrug by incorporating vitamin K3 (VK3) and Pluronic F127 to synthesize a spheroid nanoparticle (PTV-NPs). PTV-NPs with high POD content could release drugs under the ROS enrichment microenvironment in cancer cells. The released VK3 could produce abundant ROS selectively in tumor cells catalyzed by the overexpressed NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme. In turn, the resultant high ROS concentration promoted the conversion of POD dimeric prodrug to POD monomer, thereby achieving the selective killing of cancer cells with weak system toxicity. In vitro and in vivo studies consistently confirmed that PTV-NPs exhibit high drug loading potential and upstanding bioavailability. They are also effectively internalized by tumor cells, induce abundant intracellular ROS generation, and have high tumor-specific cytotoxicity. This ROS-responsive dimeric prodrug nanoplatform characterized by selective self-amplification drug release may hold promise in the field of antitumor drug delivery.
format	article
author	Bingfeng Liang Dangxia Zhou
author_facet	Bingfeng Liang Dangxia Zhou
author_sort	Bingfeng Liang
title	ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
title_short	ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
title_full	ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
title_fullStr	ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
title_full_unstemmed	ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
title_sort	ros-activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/da7bb055d1f84c14ade51f33adb8afb5
work_keys_str_mv	AT bingfengliang rosactivatedhomodimericpodophyllotoxinnanomedicinewithselfacceleratingdrugreleaseforefficientcancereradication AT dangxiazhou rosactivatedhomodimericpodophyllotoxinnanomedicinewithselfacceleratingdrugreleaseforefficientcancereradication
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ROS-Activated homodimeric podophyllotoxin nanomedicine with self-accelerating drug release for efficient cancer eradication

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