A non-destructive red blood cell retrofit strategy to construct photothermal nanoparticles for cancer therapy

Natural red blood cells (RBCs) have been recognized as highly promising drug delivery vehicles for cancer therapy, owing to their intrinsic biocompatibility, large capacity, and prolonged circulation lifetime. Traditionally, drugs are introduced into RBCs through membrane penetration or hitchhiking techniques, which often result in drug leakage or desorption and consequently adverse effects. In this study, we developed a non-destructive RBCs retrofit strategy for in situ polymerizing dopamine (DA) into polydopamine (PDA) nanoparticle within RBCs (cell membrane-polydopamine, CM-PDA). Unlike methods that involve coating nanoparticles with broken RBC membranes (BCM), this approach preserves the integrity and the mechanical properties of RBCs. As a consequence, the CM-PDA gave prolonged circulation lifetime and amplified photothermal performance compared to that was obtained with BCM-PDA. Additionally, tumor-targeting lipopeptides were attached to the surface of the CM-PDA to construct lipopeptide-modified CM-PDA (LIP-CM-PDA), further enhancing the particles' accumulation near tumor tissues. In combination with the robust photothermal performance of PDA, these LIP-CM-PDA nanoparticles exhibited excellent antitumor efficacy. The proposed intracellular polymerization strategy not only maximizes the advantages of RBCs as drug carriers, but also ensures the stability and performance of encapsulated drugs, offering significant potential for highly efficient anti-tumor therapy.