Poly(glycerol)-modified liposome for co-delivery of pheophorbide a/ topotecan and combination cancer therapy in vivo.

The clinical success of nanoparticles (NPs) with surface coating using polyethylene glycol (PEG) has been accompanied by growing concerns regarding PEG-induced hypersensitivity and immunogenicity. These limitations have spurred the search for PEG alternatives, particularly in cancer therapy, where repeated administration is common. Polyglycerol (PG), a hydrophilic and biocompatible polymer, has emerged as a promising candidate for surface coating of NPs to its antifouling properties and reduced recognition by macrophages. In this study, we developed a PG-coated liposomal nanomedicine loaded with topotecan (Tpt), a hydrophilic anticancer drug, and pheophorbide a (Pba), a hydrophobic photosensitizer. This dual-loading strategy enables two complementary therapeutic mechanisms: DNA repair inhibition by Tpt and reactive oxygen species (ROS)-mediated photodynamic therapy (PDT) by Pba under 671 nm laser irradiation. The dual drug-loaded PG-liposome (Pba/Tpt@PG) exhibited potent cytotoxicity against SCC7 tumor cells, demonstrated reduced macrophage uptake in vitro, and in vivo imaging revealed its favorable tumor accumulation. SCC7 tumor-bearing mice received intravenous injections of Pba/Tpt@PG, followed by localized laser irradiation. This treatment successfully inhibited tumor growth, reducing tumor volume to 0.58% of that in untreated controls, and outperformed single-agent treatments. No significant body weight loss or histological abnormalities were observed, indicating high biocompatibility of the materials. This study underscores the potential of dual-drug-loaded liposomes and PG-based surface modification for safe and effective combination cancer therapy.