Anti-phagocytosis and tumor cell targeting micelles prepared from multifunctional cell membrane mimetic polymers

Phagocytic clearance and inefficient targeting are two major concerns for nanomedicines in cancer therapy. In this study, cell membrane inspired multifunctional copolymers (PMNCFs) were synthesized by a combination of cell membrane stealthy hydrophilic phosphorylcholine (PC), hydrophobic cholesterol (Chol) and tumor targeting folic acid (FA) functionalities on the different side chain ends. PMNCF micelles were prepared in aqueous solution to form a cell membrane mimetic structure with linked folic acid ligands as the protruding antennae on the surface of the micelles. Coumarin-6 loaded PMNCF micelles indicated that the mouse peritoneal macrophage cell uptake efficiency was suppressed to 1/10 compared with that of PLA nanoparticles. Doxorubicin loaded micelle measurements demonstrated that up to 30% of the drug could be obtained forming a stable formulation under both storage and physiological conditions. Tumor cell uptake and toxicity studies revealed that FA-decorated PMNCF micelles could increase MADB-106 cell uptake by 4-fold, and DOX loaded PMNCF micelles could kill tumor cells more efficiently than the same amount of free DOX. These exciting results confirmed the great potential of the stable, stealthy and tumor cell targeting PMNCF micelles for developing advanced long circulation and target-selective drug delivery nanoparticles.