Glycopolymeric Photoactive Micelles for Glucose Transporter-Targeted Synergistic Combination Therapy

OpenAlex İngilizce

Drug delivery systems for cancer therapy have been investigated to alter the properties of therapeutic molecules through covalent/noncovalent interactions, lessen harmful side effects, and enhance therapeutic outcomes. Nevertheless, it is important to sustain and enhance the targeting ability of drug delivery platforms, which are beneficial to the progress of precision medicine. In the present study, a series of protoporphyrin IX (PpIX)-containing glucose and fructose-based-glycoblock copolymers were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization and click coupling reaction. Glycopolymeric photoactive micelles (GPMs) based on glycoblock copolymers (P(G/FMA l PpIX m - b - n BA n ); l = 25, m = 5, and n = 75) were prepared with antineoplastic drug loadings (paclitaxel, PTX) using a nanoprecipitation method. Glycosylated and fructosylated GPMs -GPM1–PTX and GPM2–PTX, respectively- with different diameters (127.02 and 121.20 nm) serve as suppliers of the reactive oxygen species (ROS) and PTX. This dual-engineered glyconanomedicine effectively induces synergistic interference against breast cancer owing to the dual-modal effect mediated by PpIX/PTX and glucose transporter (GLUT) targeting. Moreover, GPM1–PTX and GPM2–PTX overperformed with 4.0 and 1.8 times lower IC 50 values in cytotoxicity assays and had 3.59 and 3.55 times higher apoptosis/necrosis rates upon light irradiation when compared to that of combined free drugs formulation (PpIX + PTX) against breast cancer cells in vitro, respectively. Therefore, this work contributes to the photoactive glyconanomedicine platform in establishing the therapeutic benefit of the synergistic effect of GLUT-targeted photodynamic-chemotherapy, suggesting better therapy than monotherapy: free PpIX, and free PTX and combined free drugs formulation as well.