Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPaPEG(2K)) is utilized to achieve core-matched PEGylating modification via the pi-pi stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG(2K) shell. Compared to PCL-PEG(2K) with similar molecular weight, PPa-PEG(2K) significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Automated summary

This study demonstrates the development of a core-matched nanoassembly that shows the self-assembly capability of pure PPa molecules into NPs and the improvement of stability and antitumor activity by PPa-PEG(2K).