Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, P. R. China.
Institut Europeen des Membranes, Adaptive Supramolecular Nanosystems Group, University of Montpellier, ENSCM-CNRS, UMR5635, Place E. Bataillon CC047, 34095 Montpellier, France.
ACS Appl Mater Interfaces. 2024 Aug 28;16(34):44528-44537. doi: 10.1021/acsami.4c09548. Epub 2024 Aug 19.
The high level of accumulation of therapeutic agents in tumors is crucial for cancer treatment. Compared to the passive tumor-targeting effect, active tumor-targeting delivery systems, primarily mediated by peptides with high production costs and reduced circulation time, are highly desired. Platelet-driven technologies have opened new avenues for targeted drug delivery prevalently through a membrane coating strategy that involves intricate manufacturing procedures or the fucoidan-mediated hitchhiking method with limited platelet affinity. Here, a novel type of amphiphilic glycopolymer self-assembled micellar nanoparticle has been developed to adhere to naturally activated platelets in the blood. The simultaneous integration of fucose and sialic acid segments into glycopolymers enables closer mimicry of the structure of P-selectin glycoprotein ligand-1 (PSGL-1), thereby increasing the affinity for activated platelets. It results in the formation of glycopolymeric micelle-platelet hybrids, facilitating targeted drug delivery to tumors. The selective platelet-assisted cellular uptake of docetaxel (DTX)-loaded glycopolymeric micelles leads to lower IC values against 4T1 cells than that of free DTX. The directed tumor-targeting effect of activated platelets has significantly improved the tumor accumulation capacity of the glycopolymeric nanoparticles, with up to 21.0% found in tumors within the initial 0.2 h. Additionally, with acid-responsive drug release and inherent antimetastasis properties, the glycopolymeric nanoparticles ensured potent therapeutic efficacy, prolonged survival time, and reduced cardiotoxicity, presenting a new and unexplored strategy for platelet-directed drug delivery to tumors, showing promising prospects in treating localized tumors and preventing tumor metastasis.
治疗剂在肿瘤中的高积累水平对于癌症治疗至关重要。与被动的肿瘤靶向效应相比，主动的肿瘤靶向递药系统更受青睐，主要由生产成本高、循环时间短的肽介导。血小板驱动技术为靶向药物递药开辟了新途径，主要通过膜涂层策略，涉及复杂的制造程序或受限于血小板亲和力的岩藻糖介导的搭便车方法。在这里，开发了一种新型两亲性糖聚合物自组装胶束纳米颗粒，以粘附在血液中自然激活的血小板上。糖聚合物中同时整合岩藻糖和唾液酸片段，能够更接近地模拟 P-选择素糖蛋白配体-1（PSGL-1）的结构，从而增加对激活血小板的亲和力。这导致糖聚合物胶束-血小板杂化体的形成，有利于肿瘤的靶向药物递药。载紫杉醇（DTX）的糖聚合物胶束的选择性血小板辅助细胞摄取导致对 4T1 细胞的 IC 值低于游离 DTX。激活血小板的靶向肿瘤效应显著提高了糖聚合物纳米颗粒的肿瘤积累能力，在最初的 0.2 小时内，肿瘤中达到 21.0%。此外，具有酸响应性药物释放和固有抗转移特性，糖聚合物纳米颗粒确保了强大的治疗效果、延长的生存时间和降低的心脏毒性，为血小板导向的肿瘤药物递药提供了一种新的、未被探索的策略，在治疗局部肿瘤和预防肿瘤转移方面具有广阔的前景。
