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A tumor environment responsive doxorubicin-loaded nanoparticle for targeted cancer therapy
Zhu Q.1; Jia L.1; Gao Z.1; Wang C.1,2; Jiang H.1; Zhang J.1; Dong L.1
2014
Source PublicationMolecular Pharmaceutics
ISSN15438384
Volume11Issue:10Pages:3269
Abstract

Doxorubicin (DOX) is a potent cancer chemotherapeutic agent, but its clinical use is severely limited by potentially lethal cardiotoxicity. Delivery of DOX by particulate carriers can be an effective way to reduce its distribution in cardiac tissue. In the present study, we developed a self-assembled, tumor-microenvironment-responsive delivery system for DOX. The core of the carrier was built upon the DOX/DNA intercalation, which was further combined with cationic gelatin (C-gel) to form the complex GDD. GDD was then packaged into a complex, namely, HDD, based on the electrostatic interactions between the positively charged C-gel and negatively charged human serum albumin (HSA). The HSA molecules on the surface of the complex HDD effectively helped the particle evade the filtration of the body when injected into the circulation and passively accumulate into the tumor sites. After entering the tumor tissue, where albumin is rapidly consumed, GDD was release from HDD and the C-gel was then digested by the tumor-specific matrix metalloproteinase (MMPs) to free the DOX/DNA intercalation. Deoxyribonucleases (DNases) in the tissue could completely destroy the DNA molecules to release DOX into the microenvironments. After a series of in vitro optimization tests, we evaluated the anticancer capacity and cardiac toxicity of HDD in two animal models with cancer. The results suggested that HDD had a higher anticancer efficacy and a significantly lower cardiotoxicity than free DOX. Additionally, the main components of the carrier are all clinically approved materials. Taken together, our present delivery system is safe and efficient and has high potential for further clinical trials. © 2014 American Chemical Society.

KeywordAlbumin Encapsulated Nanoparticle Doxorubicin Tumor Environment Responsive
DOI10.1021/mp4007776
URLView the original
Indexed BySCI
Language英语
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000342857000006
The Source to ArticleScopus
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Cited Times [WOS]:29   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorZhang J.; Dong L.
Affiliation1.State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China
Recommended Citation
GB/T 7714
Zhu Q.,Jia L.,Gao Z.,et al. A tumor environment responsive doxorubicin-loaded nanoparticle for targeted cancer therapy[J]. Molecular Pharmaceutics,2014,11(10):3269.
APA Zhu Q..,Jia L..,Gao Z..,Wang C..,Jiang H..,...&Dong L..(2014).A tumor environment responsive doxorubicin-loaded nanoparticle for targeted cancer therapy.Molecular Pharmaceutics,11(10),3269.
MLA Zhu Q.,et al."A tumor environment responsive doxorubicin-loaded nanoparticle for targeted cancer therapy".Molecular Pharmaceutics 11.10(2014):3269.
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