Roussel Sabrina, Carrera Fragoso Lucia, Grenier Philippe, Bruxelles Quentin, Chénard Valérie, Marcoux Sébastien, Greffard Karine, Fortin Sébastien, Vallières Luc, Bertrand Nicolas
Faculty of Pharmacy, Université Laval, 1050 ave de la Médecine, Québec G1V 0A6, Canada.
Endocrinology and Nephrology Unit, Centre de recherche du CHU de Québec─Université Laval, CHUL building, 2705 Laurier Blvd, Québec G1V 4G2, Canada.
Biomacromolecules. 2025 May 12;26(5):2811-2824. doi: 10.1021/acs.biomac.4c01110. Epub 2025 Apr 21.
Nanomedicines modify the pharmacology of pharmaceutical ingredients, but most require cell internalization to deliver their payloads. Hence, modifying the surface properties of nanomedicines can improve their interactions with cells and modulate their pharmacology. Herein, we devised a polymer that increases how nanomedicines are internalized by cells. The alkylated poly(monoglycerol acrylate) (PMGA) polymer was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization with a terminal double 18-carbon moiety that allows its anchoring on the surface of liposomes. PMGA-decorated liposomes are internalized more efficiently in immune cells, compared to formulations without the polymer. Using inhibitors of internalization pathways, we established that PMGA promotes cell entry by the fast endophilin-mediated endocytosis (FEME). In comparison, noncoated control liposomes were mostly internalized by clathrin-mediated endocytosis. This work highlights the potential of PMGA to increase the internalization of nanomedicines by immune cells, and target a novel internalization pathway.
纳米药物可改变药物成分的药理学性质，但大多数纳米药物需要进入细胞才能递送其有效载荷。因此，改变纳米药物的表面性质可以改善它们与细胞的相互作用并调节其药理学性质。在此，我们设计了一种聚合物，它能增强纳米药物被细胞内化的程度。烷基化聚（丙烯酸单甘油酯）（PMGA）聚合物是通过可逆加成-断裂链转移（RAFT）聚合反应合成的，其末端带有双18碳基团，可使其锚定在脂质体表面。与未添加该聚合物的制剂相比，PMGA修饰的脂质体在免疫细胞中的内化效率更高。通过使用内化途径抑制剂，我们确定PMGA通过快速内吞蛋白介导的内吞作用（FEME）促进细胞摄取。相比之下，未包被的对照脂质体大多通过网格蛋白介导的内吞作用被内化。这项工作突出了PMGA在增强免疫细胞对纳米药物的内化作用以及靶向一种新的内化途径方面的潜力。
