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  • Title: Construction of a tumor microenvironment pH-responsive cleavable PEGylated hyaluronic acid nano-drug delivery system for colorectal cancer treatment.
    Author: Zhang X, Zhao M, Cao N, Qin W, Zhao M, Wu J, Lin D.
    Journal: Biomater Sci; 2020 Mar 31; 8(7):1885-1896. PubMed ID: 32022813.
    Abstract:
    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.
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