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

Shenwu Zhang; Yuequan Wang; Zhiqiang Kong; Xuanbo Zhang; Bingjun Sun; Han Yu; Qin Chen; Cong Luo; Jin Sun; Zhonggui He

doi:10.1016/j.apsb.2021.04.005

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

Acta Pharm Sin B. 2021 Nov;11(11):3636-3647. doi: 10.1016/j.apsb.2021.04.005. Epub 2021 Apr 20.

Authors

Shenwu Zhang¹, Yuequan Wang¹, Zhiqiang Kong¹, Xuanbo Zhang¹, Bingjun Sun¹, Han Yu¹, Qin Chen², Cong Luo¹, Jin Sun¹, Zhonggui He¹

Affiliations

¹ Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
² Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.

Abstract

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 (PPa-PEG_2K) is utilized to achieve core-matched PEGylating modification via the π‒π 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.

Keywords: ACQ, aggregation caused quenching; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urine nitrogen; CRE, creatinine; Core-matched; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; DDS, drug delivery system; FBS, fetal bovine serum; Imaging-guided; NPs, nanoparticles; NaCl, sodium chloride; Nanoassembly; PBS, phosphate buffer solution; PDANs, pure drug-assembled nanomedicines; PDT, photodynamic therapy; PPa, pyropheophorbide a; PS, photosensitizer; Photodynamic therapy; Pure drug-assembled nanomedicines; Pure photosensitizer; Pyropheophorbide a; ROS, reactive oxygen species; SDS, sodium dodecyl sulfate; SOSG, Singlet Oxygen Sensor Green Reagent; Self-assembly; nano-DDS, nanoparticulate drug delivery systems.