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

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.