Malinovskaya Julia, Kovshova Tatyana, Melnikov Pavel, Li Zhuoxuan, Dhakal Namrata, Knoll Julian, Valikhov Marat, Ermolenko Yulia, Chernysheva Anastasia, Gurina Olga, Chekhonin Vladimir, Wacker Matthias G, Gelperina Svetlana
D. Mendeleev University of Chemical Technology of Russia, Miusskaya pl. 9, 125047, Moscow, Russia.
Department of Neurobiology, V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian Federation, Kropotkinskiy per. 23, 119034, Moscow, Russia.
J Control Release. 2025 Feb 10;378:750-762. doi: 10.1016/j.jconrel.2024.12.056. Epub 2024 Dec 29.
Poly(lactide-co-glycolide) (PLG) nanoparticles loaded with doxorubicin have reached phase-I clinical trials for treating advanced solid tumors. This study explores cell hitchhiking, where nanoparticles associate with blood cells and investigates the impact on pharmacokinetics and tumor migration. Previous findings highlighted the early post-injection phase dominated by nonspecific nanoparticle-cell interactions and burst release. In contrast, this study examines the subsequent phase of tumor invasion, emphasizing the role of immune cells, mostly neutrophils, in redistributing the carrier to the tumor site via blood cell hitchhiking. We provide a detailed investigation of nanoparticle extravasation kinetics and mechanisms, showing qualitative and quantitative evidence of increased nanoparticle association with immune cells over time. By 30 min post-injection, approximately 15 % of monocytes and 15-19 % of neutrophils tested positive for nanoparticles, with significant differences observed between ex vivo and in vivo experiments, and between healthy and tumor-bearing animals. This study underscores the ambiguous role of immune cell-mediated tumor targeting. While the total accumulation of the carrier rises, this fraction is partially trapped in immune cells without any chance to escape.
负载阿霉素的聚（丙交酯-共-乙交酯）（PLG）纳米颗粒已进入治疗晚期实体瘤的I期临床试验。本研究探索了细胞搭便车现象，即纳米颗粒与血细胞结合，并研究其对药代动力学和肿瘤迁移的影响。先前的研究结果强调了注射后早期阶段以非特异性纳米颗粒-细胞相互作用和突释为主。相比之下，本研究考察了肿瘤侵袭的后续阶段，强调免疫细胞（主要是中性粒细胞）通过血细胞搭便车将载体重新分布到肿瘤部位的作用。我们对纳米颗粒外渗动力学和机制进行了详细研究，显示了随着时间推移纳米颗粒与免疫细胞结合增加的定性和定量证据。注射后30分钟，约15%的单核细胞和15 - 19%的中性粒细胞检测出纳米颗粒呈阳性，体外和体内实验之间以及健康动物和荷瘤动物之间均观察到显著差异。本研究强调了免疫细胞介导的肿瘤靶向作用的模糊性。虽然载体的总积累量增加，但这一部分被部分困在免疫细胞中，没有任何逃脱的机会。
