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<p>The therapeutic efficacy of hepatocellular carcinoma (HCC) medication is severely compromised by inadequate drug delivery to tumor sites. Herein, we fabricated a biomimetic nanoplatform for improved drug targeting ability by wrapping H22 tumor cell membranes around natural chalk to encapsulate the model drug doxorubicin (C-DOX@H22 CM). When camouflaged with H22 tumor cell membranes, C-DOX@H22 CM achieved primary targeting to the tumor tissues due to the immune escape ability and secondary deep targeting to HCC cells owing to the homologous targeting properties. The cellular uptake of C-DOX@H22 CM by H22 cells was via clathrin-mediated endocytosis. Meanwhile, C-DOX@H22 CM exhibited the property of deep penetration into dense tumor tissues. Moreover, the pH-responsive characteristics of the natural chalk enabled C-DOX@H22 CM to achieve endosomal escape and drug release, thereby expanding its antitumor effects without compromising biocompatibility. Importantly, the in vivo experiments also confirmed that C-DOX@H22 CM had favorable antitumor efficacy and biosafety in the H22 tumor-bearing mouse model. Overall, the novel C-DOX@H22 CM nanoplatform provides a safe and effective treatment option for HCC and has the potential to achieve clinical translation for the targeted delivery of other drugs for the treatment of various tumors.</p>

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Homologous cancer cell membrane-camouflaged natural pH-sensitive chalk for enhanced drug targeting delivery in hepatocellular carcinoma

  • 期刊论文

  • 发表日期：

    2025年7月21日

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  • Yangbo Zhu,
  • Pengfei Cui,
  • Lijuan Zhao,
  • Qi Ling,
  • Jiayi Qin

摘要

The therapeutic efficacy of hepatocellular carcinoma (HCC) medication is severely compromised by inadequate drug delivery to tumor sites. Herein, we fabricated a biomimetic nanoplatform for improved drug targeting ability by wrapping H22 tumor cell membranes around natural chalk to encapsulate the model drug doxorubicin (C-DOX@H22 CM). When camouflaged with H22 tumor cell membranes, C-DOX@H22 CM achieved primary targeting to the tumor tissues due to the immune escape ability and secondary deep targeting to HCC cells owing to the homologous targeting properties. The cellular uptake of C-DOX@H22 CM by H22 cells was via clathrin-mediated endocytosis. Meanwhile, C-DOX@H22 CM exhibited the property of deep penetration into dense tumor tissues. Moreover, the pH-responsive characteristics of the natural chalk enabled C-DOX@H22 CM to achieve endosomal escape and drug release, thereby expanding its antitumor effects without compromising biocompatibility. Importantly, the in vivo experiments also confirmed that C-DOX@H22 CM had favorable antitumor efficacy and biosafety in the H22 tumor-bearing mouse model. Overall, the novel C-DOX@H22 CM nanoplatform provides a safe and effective treatment option for HCC and has the potential to achieve clinical translation for the targeted delivery of other drugs for the treatment of various tumors.