Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 6, Issue 7, Pages 4106-4115Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c00762
Keywords
hyaluronic acid; prodrug micelles; self-assembly; redox-responsive; drug delivery
Categories
Funding
- National Natural Science Foundation of China [21905069]
- Shenzhen Science and Technology Innovation Committee [JCYJ20180507183907224, KQTD20170809110344233]
- Economic, Trade and Information Commission of Shenzhen Municipality through the Graphene Manufacture Innovation Center [201901161514]
- Guangdong Province Covid19 Pandemic Control Research Fund [2020KZDZX1220]
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Currently, available nanoscale anticancer drug delivery systems have low targeting and release efficiency, limiting their therapeutic effects. Thus, tumor-targeting nanocarriers for self-assembly of amphiphilic polymer-drug conjugates are urgently needed to improve drug targeting and treatment efficacy. Here, we report the construction of a stable, reduction-sensitive prodrug conjugate based on hyaluronic acid-grafted pH-sensitive doxorubicin (DOX). The amphiphilic prodrug copolymer self-assembled into spherical nanoparticles in aqueous solution and exhibited an average diameter of 150 nm. Prodrug micelles were stable in a normal physiological environment and achieve selective and rapid release under acidic pH and/or high reduction conditions. Cell Counting Kit-8, flow cytometry, and live cell imaging assays showed that the prodrug had high targeting and antitumor activity against CD44 receptors. Moreover, in vivo pharmacokinetics and biodistribution studies showed that the prodrug had a longer circulation time in BALB/c mice and higher accumulation in 4T1 tumors. Interestingly, the prodrug could effectively treat tumors with few side effects. These results showed that the DOX prodrug micelles developed in this study may have great potential in targeted therapy.
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