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Type: Journal article
Title: HPMA polymeric nanocarriers for anticancer drugs with tumor microenvironment-responsive extracellular biodegradation and intracellular drug release
Author: Zhou, M.
Tang, M.
Zhang, H.
Luo, K.
Huang, Y.
Citation: Journal of Biomedical Nanotechnology, 2019; 15(8):1688-1700
Publisher: American Scientific Publishers
Issue Date: 2019
ISSN: 1550-7033
Statement of
Zhou, Minglu,Tang Manling, Zhang Hu, Luo Kui, Huang Yuan
Abstract: The balance between systemic toxicity and circulation time for a polymeric nanocarrier to deliver antitumor drugs has been trialed. A new approach to break the balance was proposed in this study by significantly improving its biosafety and prolonging the circulation time, hence, to enhance its anti-tumor efficacy. A matrix metalloproteinases (MMPs)-sensitive peptide (PVGLIGK) was introduced to cross-link the N-(2-hydroxypropyl) methylacrylamide polymer-doxorubicin conjugates (HPMA-Dox) conjugate to construct a nano-size polymeric nanocarrier-Dox assembly (PMD) with a molecular weight (MW) of 73 kDa and this modification has resulted in a prolonged circulation time (a half-time of 20.1 h) and enhanced accumulation of PMD at the tumor site, while negligible systemic toxicity and excellent biocompatibility were displayed after injection of PMD into the mice. The cross-linked nanoassembly was unpacking in the presence of MMPs in the extracellular microenvironment, and the conjugated Dox was released from the nanoassembly in the lysosome/endosome due to an intracellular low pH microenvironment. The released Dox from PMD inhibited tumor cells very efficiently with a tumor growth inhibition of around 70%. The outstanding performance of the dual stimuli-responsive biodegradable polymeric nanocarriers may open a door for other hydrophobic anti-tumor drugs.
Keywords: Antitumor; biodegradation; extracellular microenvironment-responsive; HPMA copolymer; intracellular microenvironment-responsive; matrix metalloproteinases
Rights: Copyright status unknown
DOI: 10.1166/jbn.2019.2727
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Chemical Engineering publications

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