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Issue 4, 2018
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Synthesis of enzyme-responsive phosphoramidate dendrimers for cancer drug delivery

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Abstract

Stimuli-responsive dendrimers are attractive nanocarriers for cancer drug delivery due to their inherent structure, biodegradability and precise control of release of a payload in response to specific triggers. However, the efficient and precise synthesis of such dendrimers with site-specific responsiveness is challenging. We report an efficient synthesis of enzyme-responsive phosphoramidate (PAD) dendrimers from a pair of monomers using click and click-like reactions. These dendrimers were stable in phosphate buffered saline (PBS) but degradable in the presence of phospholipase C (PLC) that was overexpressed on cancer cells. The surface modification of the dendrimers with zwitterionic groups (2-methacryloyloxyethyl phosphorylcholine, MPC) greatly reduced the nonspecific binding of the plasma proteins and therefore enhanced blood circulation time. The PAD-MPC dendrimers easily encapsulated hydrophobic drugs such as doxorubicin (DOX). The DOX-loaded PAD-MPC (PAD-MPC/DOX) showed PLC-responsive drug release and efficient delivery of DOX to cancer cells by overcoming multidrug resistance. The PLC-responsive PAD-MPC/DOX was highly toxic to cancer cells and less effective on normal cells. The PAD-MPC/DOX showed improved therapeutic effects and reduced toxicity in athymic nude mice bearing xenografts of MCF-7/ADR breast cancer.

Graphical abstract: Synthesis of enzyme-responsive phosphoramidate dendrimers for cancer drug delivery

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Publication details

The article was received on 02 Sep 2017, accepted on 16 Dec 2017 and first published on 18 Dec 2017


Article type: Paper
DOI: 10.1039/C7PY01492A
Citation: Polym. Chem., 2018,9, 438-449
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    Synthesis of enzyme-responsive phosphoramidate dendrimers for cancer drug delivery

    Z. Zhang, Y. Zhou, Z. Zhou, Y. Piao, N. Kalva, X. Liu, J. Tang and Y. Shen, Polym. Chem., 2018, 9, 438
    DOI: 10.1039/C7PY01492A

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