Molecular Dynamics Simulations of Hybrid Cell Membrane‐Coated Porphyrin Nanoparticles for Enhanced Photochemotherapy of Breast Cancer

Abstract The construction of a bionic membrane drug delivery system introduces new opportunities and challenges for cancer treatment. Cell membrane‐coated nanoparticles can maintain inherent cellular properties, such as homologous homing, and enhance the stability of nanoparticles in a complex blood environment. In this study, a porphyrin carrier (Por) is designed and synthesized to assemble with doxorubicin (Dox) to construct Dox‐Por nanomicelles guided by computational simulations. The mouse breast cancer cell membrane (4T1‐M) and red blood cell membrane (RBC‐M) are fused to create a hybrid biomimetic membrane (TRM), which is subsequently camouflaged on Dox‐Por, resulting in Dox‐Por@TRM. This construct exhibits high drug loading, specific self‐recognition of 4T1 cells, and prolonged blood circulation time. Both in vitro and in vivo anti‐tumor assessments demonstrates that Dox‐Por@TRM has enhanced combination therapy effects and can eliminate subcutaneous tumors with a single dose and three laser irradiations. These findings provide a feasible and effective strategy for the combined therapy of photodynamic and chemotherapy.