Regulating Interactions Between Targeted Nanocarriers and Mononuclear Phagocyte System via an Esomeprazole-Based Preconditioning Strategy
Regulating Interactions Between Targeted Nanocarriers and Mononuclear Phagocyte System via an Esomeprazole-Based Preconditioning Strategy
复制标题
通过基于埃索美拉唑的预处理策略调节靶向纳米载体和单核吞噬细胞系统之间的相互作用
DOI：
10.2147/ijn.s258054
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发表时间：
2020-01-01
影响因子：
8
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Belhadj, Zakia;He, Bing;Zhang, Qiang
目的单核巨噬细胞系统（MPS）是阻碍各种纳米制剂向肿瘤递送的一个巨大障碍。因此，迫切需要提高纳米药物的非MPS靶向能力。在本研究中，我们提出了一种新的预处理策略，通过调节纳米载体-MPS相互作用来显著增加纳米颗粒的循环时间和肿瘤靶向。方法在体外实验中，观察不同的液泡H+-ATP酶抑制剂对巨噬细胞摄取靶向或非靶向脂囊泡的影响。具体而言，选择临床批准的质子泵抑制剂埃索美拉唑（ESO）作为预处理剂。然后，我们进一步研究了ESO对纳米载体的巨噬细胞内吞作用的阻断作用。在体内，首先将ESO静脉内给予荷A549肿瘤的裸鼠，24 h后，静脉内注射c（RGDM 7）修饰的囊泡，共负载阿霉素和吉非替尼。结果ESO通过干扰c（RGDM 7）修饰囊泡的溶酶体运输，降低了c（RGDM 7）修饰囊泡与巨噬细胞的相互作用。在体内进行的研究证实，ESO预处理大大减少了靶向囊泡的肝脏和脾脏分布，增强了它们的肿瘤积累，并改善了载药纳米药物的治疗效果。结论ESO可以调控纳米粒与MPS的相互作用，为增强纳米药物的非MPS靶向性提供了一种可行的选择。
Purpose The mononuclear phagocyte system (MPS) presents a formidable obstacle that hampers the delivery of various nanopreparations to tumors. Therefore, there is an urgent need to improve the off-MPS targeting ability of nanomedicines. In the present study, we present a novel preconditioning strategy to substantially increase the circulation times and tumor targeting of nanoparticles by regulating nanocarrier-MPS interactions. Methods In vitro, the effect of different vacuolar H+-ATPase inhibitors on macrophage uptake of targeted or nontargeted lipid vesicles was evaluated. Specifically, the clinically approved proton-pump inhibitor esomeprazole (ESO) was selected as a preconditioning agent. Then, we further investigated the blocking effect of ESO on the macrophage endocytosis of nanocarriers. In vivo, ESO was first intravenously administered into A549-tumor-bearing nude mice, and 24 h later, the c(RGDm7)-modified vesicles co-loaded with doxorubicin and gefitinib were intravenously injected. Results In vitro, ESO was found to reduce the interactions between macrophages and c(RGDm7)-modified vesicles by interfering with the latter’s lysosomal trafficking. Studies conducted in vivo confirmed that ESO pretreatment greatly decreased the liver and spleen distribution of the targeted vesicles, enhanced their tumor accumulation, and improved the therapeutic outcome of the drug-loaded nanomedicines. Conclusion Our findings indicate that ESO can regulate the nanoparticle-MPS interaction, which provides a feasible option for enhancing the off-MPS targeting of nanomedicines.