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Regulating Interactions Between Targeted Nanocarriers and Mononuclear Phagocyte System via an Esomeprazole-Based Preconditioning Strategy.
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-08-25 , DOI: 10.2147/ijn.s258054
Zakia Belhadj 1 , Bing He 1 , Jijun Fu 2 , Hua Zhang 1 , Xueqing Wang 1 , Wenbing Dai 1 , Qiang Zhang 1
Affiliation  

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.

Keywords: mononuclear phagocyte system, preconditioning strategy, esomeprazole, V-ATPase inhibitors, targeted lipid vesicles


中文翻译:

通过基于埃索美拉唑的预处理策略调节靶向纳米载体与单核吞噬细胞系统之间的相互作用。

目的:单核吞噬细胞系统 (MPS) 是一个巨大的障碍,阻碍了各种纳米制剂向肿瘤的输送。因此,迫切需要提高纳米药物的off-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 的相互作用来显着增加纳米颗粒的循环时间和肿瘤靶向性。
方法:在体外,不同液泡H +的作用-评估了靶向或非靶向脂质囊泡巨噬细胞摄取的ATP酶抑制剂。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对纳米载体巨噬细胞内吞作用的阻断作用。在体内,首先将 ESO 静脉注射到携带 A549 肿瘤的裸鼠中,24 小时后,静脉注射含有多柔比星和吉非替尼的 c(RGDm7) 修饰的囊泡。
结果:在体外,发现 ESO 通过干扰后者的溶酶体运输来减少巨噬细胞和 c(RGDm7) 修饰的囊泡之间的相互作用。体内研究证实,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:我们的研究结果表明,ESO 可以调节纳米颗粒-MPS 的相互作用,这为增强纳米药物的非 MPS 靶向提供了可行的选择。

关键词:单核吞噬细胞系统,预处理策略,埃索美拉唑,V-ATP酶抑制剂,靶向脂质囊泡
更新日期:2020-08-25
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