Preparation and characterization of macrophage membrane camouflaged cubosomes as a stabilized and immune evasive biomimetic nano-DDS†

Abstract

This study aims to develop a biomimetic nano-drug delivery system (nano-DDS) by employing a macrophage cell membrane camouflaging strategy to modify lyotropic liquid crystal nanoparticles (LLC-NPs). The cubic-structured LLC-NPs (Cubosomes, CBs) were prepared via a top-down approach (ultra-sonification) using monoolein (MO) and doped with the cationic lipid, DOTAP. The cell membrane camouflaging procedure induced changes in the cubic lipid phase from primitive cubic phase (Q_II^P) to a coexistence of Q_II^P and diamond cubic phase (Q_II^D). The macrophage membrane camouflaging strategy protected CB cores from the destabilization by blood plasma and enhanced the stability of CBs. The in vitro experiment results revealed that the macrophage cell membrane coating significantly reduced macrophage uptake efficacy within 8 h of incubation compared to the non-camouflaged CBs, while it had minimal impact on cancer cell uptake efficacy. The macrophage membrane coated CBs showed lower accumulation in the heart, kidney and lungs in vivo. This study demonstrated the feasibility of employing cell membrane camouflaging on CBs and confirmed that the bio-functionalities of the CBs-based biomimetic nano-DDS were retained from the membrane source cells, and opened up promising possibilities for developing an efficient and safe drug delivery system based on the biomimetic approach.