Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer

Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens,including prolonged circulation in the bloodstream,specific cell recognition and targeting capabilities,and potential for immunotherapy.Herein,we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM NPs.Comprising microporous Prussian blue nanoparticles(MPB NPs)serving as both a photothermal sensitizer and carrier for 3-bromopyruvate(3BP),these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory proteinα(SIRPα)with enhanced affinity to CD47.As a result,MPB-3BP@CM NPs inherit the characteristics of the original cell membrane,exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer(CRC)cells.Notably,blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by macrophages.Additionally,3BP,an inhibitor of hexokinase II(HK2),suppresses glycolysis,leading to a reduction in adenosine triphosphate(ATP)levels and lactate production.Besides,it promotes the polarization of tumor-associated macrophages(TAMs)towards an anti-tumor M1 phenotype.Furthermore,integration with MPB NPs-mediated photothermal therapy(PTT)enhances the therapeutic efficacy against tumors.These advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for CRC.Concurrently,it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.