Cell membrane-inspired chitosan nanoparticles for prolonged circulation and tumor-targeted drug delivery

Conventional chemotherapy is challenged by its inherent limitations. As an emerging drug delivery system, nanoparticles are easily eliminated by the immune system due to their exogenous nature. Moreover, the lack of long-circulation and tumor-targeting greatly limits their application. In our research, to address this problem, the biomimetic nanocarriers combine cell membranes, targeting ligand and nanoparticles into one system. Firstly, an active ester monomer and three terpolymers PMAN containing different proportions of phosphorylcholine, sulfonic acid and active ester group were successfully synthesized. Subsequently, aminated-folate was synthesized and grafted onto the terpolymers to prepare the folate-targeted polymers FA-PMAN. Finally, cell membrane biomimetic and folate-targeted chitosan nanoparticles (FA-PMAN/CS) with average particle size of 100 to 200 nm were prepared through electrostatic interactions. The in vivo blood circulation results showed that the long-circulating properties of PMAN/CS nanoparticles were significantly enhanced, compared with TPP/CS nanoparticle as a control. The half-life extended from 2.71 h to 12.95 h, with five-fold increase. Additionally, the uptake efficiency of FA-PMAN/CS nanoparticles by rat breast cancer cells (MADB-106) was 5-6 times greater than that of nanoparticles without folate. The biological distribution in mice demonstrated that the signal intensity in tumors treated with FA-PMAN/CS nanoparticle was substantially higher than in other organs, indicating that folate on the surface of nanoparticles increased the uptake into cancer cells. This work aims to design more efficient nanocarriers through biomimetic simulation of cell membranes, reduce recognition and clearance by the immune system, prolong blood circulation time and achieve tumor-targeted drug delivery. It is expected to significantly improve efficacy and provide an innovative strategy for clinical treatment.