Construction of a Tumor Microenvironment Ph-Responsive Cleavable Pegylated Hyaluronic Acid Nano-Drug Delivery System for Colorectal Cancer Treatment

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作者：Zhang, X., Zhao, M., Cao, N., Qin, W., Zhao, M., Wu, J. & Lin, D.
期刊：Biomaterials science 8, 1885-1896 (2020)
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In order to improve active tumor targeting, tumor cell uptake efficiency and circulation time of doxorubicin (DOX) in vivo, we constructed a cleavable PEGylated hyaluronic acid nano-drug delivery system (HA-mPEG2k-DOX) based on a tumor microenvironment pH-responsive imine bond. In this study, HA-mPEG2k-DOX can self-assemble into stable nanoparticles (HA-mPEG2k-DOX NPs) with a particle size of 50 nm. And the NPs can efficiently target CD44 positive CT26 cells and the pH-responsive cleavable PEG shell can be detached under weakly acidic environments and effectively promote the cellular uptake of HA-DOX NPs. Compared with DOX·HCl, the HA-mPEG2k-DOX NPs can significantly increase the DOX circulation time by 12.5 times, efficiently target the tumor tissues of CT26 tumor-bearing mice and remain for 72 hours. Therefore, the antitumor results in vivo indicated that the HA-mPEG2k-DOX NPs have the best anti-tumor effect while reducing the toxicity of the DOX. Overall, the cleavable PEGylated HA-mPEG2k-DOX NPs responding to pH-sensitive imine bonds, while actively targeting CD44-positive tumor cells, improve the dilemma of cellular uptake and delivery by the PEGylated nano delivery system.