摘要The therapeutic efficacy of hepatocellular carcinoma(HCC)medication is severely compromised by inadequate drug deliv-ery 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 camou-flaged 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 nanoplat-form provides a safe and effective treatment option for HCC and has the potential to achieve clinical translation for the tar-geted delivery of other drugs for the treatment of various tumors.