Photolytic Removal of Red Blood Cell Membranes Camouflaged on Nanoparticles for Enhanced Cellular Uptake and Combined Chemo-Photodynamic Inhibition of Cancer Cells

Biomimetic therapeutics offer great potential for drug delivery that avoids immune recognition. However, the coated cell membrane usually hinders the cellular uptake of nanoparticles; thus, structure-changeable formulations have attracted increasing attention. Herein, we report photolytic pyropheophorbide a (PA)-inserted red blood cell (RBC) membrane-camouflaged curcumin dimeric prodrug (CUR₂-TK)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles [(CUR₂-TK)-PLGA@RBC-PA] for enhanced Cancer therapy. In these nanoparticles, the inner core was constructed using PLGA and loaded with our synthesized Reactive Oxygen Species (ROS)-responsive cleavable curcumin dimeric prodrug (CUR₂-TK). The nanoparticles generated ROS in response to the light irradiation attributed to the incorporated PA. The ROS further triggered the lysis of the cell membrane and exposed the nanoparticles for enhanced tumor cellular uptake, and the ROS also cleaved CUR₂-TK for controlled CUR drug release. Moreover, the ROS performed photodynamic therapy (PDT). The chemotherapy and PDT produced a combined effect in the treatment of Cancer cells, thus enhancing Anticancer therapeutic efficacy.