Photosensitizer-loaded cell membrane biomimetic nanoparticles for enhanced tumor synergetic targeted therapy

Photodynamic therapy (PDT) has the advantages of low toxicity and specificity, but photosensitizers usually fail to accumulate efficiently at the tumor site. In this study, a new multifunctional nano-drug delivery system was exploited by a biomimetic strategy to improve the PDT effects. The self-assembled methoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA) nanoparticles encapsulated with the photosensitizer chlorin e6 (Ce6) by microfluidics were employed as the nano-core, followed by coating red blood cell (RBC) membranes as the biomimetic agent to prolong the circulation time in vivo. In order to boost the therapeutic effect, doxorubicin (Dox) was preloaded into RBC nanovesicles. The cell membrane surface was modified with folic acid (FA) to further enhance the tumor targeting efficiency. The prepared biomimetic nanoparticles with a homogeneous size (70 nm) can trigger sufficient reactive oxygen species (ROS), leading to significant tumor ablation without side effects. In addition, the system had high tumor targeting efficiency, with an increase of 25% compared with no FA-modified nanoparticles. Therefore, this biomimetic multifunctional nanodrug delivery system possesses a prolonged circulation time and higher tumor targeting efficiency and can exert better tumor cytotoxicity for improved PDT due to homophilic targeting in vivo.