Glycopolymeric Micellar\nNanoparticles for Platelet-Mediated\nTumor-Targeted Delivery of Docetaxel for Cancer Therapy

The high level of accumulation of therapeutic agents\nin tumors\nis crucial for cancer treatment. Compared to the passive tumor-targeting\neffect, active tumor-targeting delivery systems, primarily mediated\nby peptides with high production costs and reduced circulation time,\nare highly desired. Platelet-driven technologies have opened new avenues\nfor targeted drug delivery prevalently through a membrane coating\nstrategy that involves intricate manufacturing procedures or the fucoidan-mediated\nhitchhiking method with limited platelet affinity. Here, a novel type\nof amphiphilic glycopolymer self-assembled micellar nanoparticle has\nbeen developed to adhere to naturally activated platelets in the blood.\nThe simultaneous integration of fucose and sialic acid segments into\nglycopolymers enables closer mimicry of the structure of P-selectin\nglycoprotein ligand-1 (PSGL-1), thereby increasing the affinity for\nactivated platelets. It results in the formation of glycopolymeric\nmicelle–platelet hybrids, facilitating targeted drug delivery\nto tumors. The selective platelet-assisted cellular uptake of docetaxel\n(DTX)-loaded glycopolymeric micelles leads to lower IC<sub>50</sub> values against 4T1 cells than that of free DTX. The directed tumor-targeting\neffect of activated platelets has significantly improved the tumor\naccumulation capacity of the glycopolymeric nanoparticles, with up\nto 21.0% found in tumors within the initial 0.2 h. Additionally, with\nacid-responsive drug release and inherent antimetastasis properties,\nthe glycopolymeric nanoparticles ensured potent therapeutic efficacy,\nprolonged survival time, and reduced cardiotoxicity, presenting a\nnew and unexplored strategy for platelet-directed drug delivery to\ntumors, showing promising prospects in treating localized tumors and\npreventing tumor metastasis.