Anti-hepatoma effect of homologous delivery of doxorubicin by HepG2 cells

Compared to conventional polymer-based and biomaterial carriers, cells as vehicles for delivering bioactive molecules in the treatment of tumor diseases offer characteristics such as non-toxicity, biocompatibility, low immunogenicity, and prolonged in vivo circulation. However, the focus of current cell drug delivery systems predominantly lies on live cells, such as red blood cells, white blood cells and others. Here, a drug delivery strategy targeting liver cancer utilizing cryo-shocked liver cancer cells (HepG2) as carriers was presented, and non-proliferative HepG2 cells particles loaded with DOX (HepG2-DOX) was effectively prepared, which has good homologous targeting. Subsequent in vitro and in vivo experiments demonstrated the non-proliferative and non-pathogenic nature of this drug delivery system. The outcomes of in vitro experiments revealed that the inhibitory effect of HepG2-DOX on HepG2 was approximately five times higher than that of free DOX, with the IC₅₀ value of HepG2-DOX being 0.0739 µg/mL and free DOX being 0.3606 µg/mL. Furthermore, in comparison to the positive DOX group, the HepG2-DOX group has a very significant advantage in tumor inhibition rate (91.34 % vs. 64.20 %). Cell uptake experiments indicated significant HepG2-DOX uptake by HepG2 cells compared to 4T1, LO2, and Raw cell groups, highlighting the excellent cell specificity of HepG2-DOX. Fluorescence imaging conducted in mice following the administration of HepG2-DOX demonstrated prompt drug localization within the tumor region, highlighting exceptional in vivo targeting precision. To sum up, this study introduced a novel strategy utilizing cryo-shocked liver cancer cells as a drug delivery system, effectively treating liver tumor by enhancing tumor targeting specificity.