Glycopolymeric Photosensitizers with Cholic Acid for HepG2-Targeted Chemo-Photodynamic Synergistic Therapy

The aggregation-caused quenching, premature drug release, and hypoxia-caused resistance of photodynamic therapy (PDT) are challenges in the design and preparation of novel porphyrin-containing photosensitizers. In this work, a series of block copolymers consisting of a hydrophilic glycopolymer block and a porphyrin-containing hydrophobic block were prepared via reversible addition-fragmentation chain transfer polymerization. The polymeric photosensitizers generate singlet oxygen and excellent PDT against HepG2, which can be strengthened by the addition of cholic acid. To combine with chemotherapy, doxorubicin (Dox) was successfully loaded into copolymers, which were observed to be more phototoxic, indicating that the therapeutic benefit of the synergistic effect of PDT and chemotherapy is better than their simple combination. The sugar-cell-specific interaction of galactose-containing photosensitizers results in a stronger mean fluorescent index (MFI) intracellular uptake in HepG2 cells in vitro compared to L929 and MCF-7 cells. These polymeric nanoplatforms present a versatile and effective avenue for developing synergistic therapy for cancer treatment.

Automated summary

In this study, block copolymers consisting of a hydrophilic glycopolymer block and a porphyrin-containing hydrophobic block were prepared via reversible addition-fragmentation chain transfer polymerization. These polymeric photosensitizers generate singlet oxygen and show excellent photodynamic therapy (PDT) effects against HepG2 cells. By combining with the chemotherapy drug Doxorubicin (Dox), the polymeric copolymers exhibit enhanced phototoxicity, indicating the superior therapeutic benefit of the synergistic effect of PDT and chemotherapy. The galactose-containing photosensitizers exhibit a stronger intracellular uptake in HepG2 cells compared to L929 and MCF-7 cells, showing their potential for targeted cancer therapy.