Less is More: Biomimetic Hybrid Membrane Nanocarriers for Highly Efficient Tumor Targeted Drug Delivery

Abstract Biomimetic camouflaged nanocarriers coated with cancer cell membranes (CCMs) have attracted considerable research attention for drug delivery application. CCM‐camouflaged nanocarriers have inherent tumor‐homologous targeting ability. However, they enter cancer cells via endocytosis, which is not efficient for drug delivery. Switching the internalization mechanism to membrane fusion may enhance their delivery efficiency. In this study, an innovative biomimetic‐targeting nanocarrier is designed by hybridizing CCMs with pH‐sensitive liposomes (1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine liposomes, DOPE‐Lipo), named as CCMpHD. The presence of CCMs makes the nanocarriers capable of homologous targeting, and the DOPE‐Lipo hybrid allows the nanocarriers to achieve efficient internalization via membrane fusion. Notably, the cellular uptake of CCMpHD is significantly higher than that of the CCMs. The most efficient delivery is achieved with 1/10 CCMs, which requires remarkably less cell membranes. Doxorubicin (DOX) is used as a model drug to characterize the homologous targeting drug delivery properties of the hybrid nanocarriers. Both in vitro and in vivo experiments demonstrated that the nanocarriers exhibited satisfactory biosafety and enhanced tumor‐targeted delivery. With enhanced delivery efficiency whilst requiring fewer CCMs, these hybrid membrane nanocarriers provides a new strategy for CCM‐based drug delivery in cancer treatment.