Enhancing Targeted Photodynamic Therapy: Star-Shaped Glycopolymeric Photosensitizers for Improved Selectivity and Efficacy

Targeted photodynamic therapy (PDT) offers advantages over nontargeted approaches, including improved selectivity, efficacy, and reduced side effects. This study developed star-shaped glycopolymeric photosensitizers using porphyrin-based initiators via ATRP. Incorporating a porphyrin core gave the polymers fluorescence and ROS generation, while adding fructose improved solubility and targeting capabilities. The photosensitizers had high light absorption, singlet oxygen production, specificity, low dark toxicity, and biocompatibility. The glycopolymers with longer sugar arms and higher density showed better uptake on MCF-7 and MDA-MB-468 cells compared to HeLa cells, indicating enhanced targeting capabilities. Inhibition of endocytosis confirmed the importance of the GLUT5 receptor. The resulting polymers exhibited good cytocompatibility under dark conditions and satisfactory PDT under light irradiation. Interestingly, the polymers containing fructose have a GLUT5-dependent elimination effect on the MCF-7 and MDA-MB-468 cells. The intracellular ROS production followed a similar pattern, indicating that the fructose polymer exhibits specific targeting toward cells with GLUT5 receptors.