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Enhancement of the blood-circulation time and performance of nanomedicines via the forced clearance of erythrocytes.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2020-07-06 , DOI: 10.1038/s41551-020-0581-2
Maxim P Nikitin 1 , Ivan V Zelepukin 1, 2 , Victoria O Shipunova 1, 2 , Ilya L Sokolov 1 , Sergey M Deyev 2 , Petr I Nikitin 3
Affiliation  

The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system limits the activity of many nanoparticle formulations. Here, we show that inducing a slight and transient depletion of erythrocytes in mice (~5% decrease in haematocrit) by administrating a low dose (1.25 mg kg−1) of allogeneic anti-erythrocyte antibodies increases the circulation half-life of a range of short-circulating and long-circulating nanoparticle formulations by up to 32-fold. Treatment of the animals with anti-erythrocyte antibodies significantly improved the targeting of CD4+ cells in vivo with fluorescent anti-CD4-antibody-conjugated nanoparticles, the magnetically guided delivery of ferrofluid nanoparticles to subcutaneous tumour allografts and xenografts, and the treatment of subcutaneous tumour allografts with magnetically guided liposomes loaded with doxorubicin and magnetite or with clinically approved ‘stealthy’ doxorubicin liposomes. The transient and partial blocking of the mononuclear phagocyte system may enhance the performance of a wide variety of nanoparticle drugs.



中文翻译:

通过强制清除红细胞,增强血液循环时间和纳米药物的性能。

单核吞噬细胞系统从血流中快速清除纳米颗粒,限制了许多纳米颗粒制剂的活性。在这里,我们表明,通过给予低剂量(1.25 mg kg -1)的同种异体抗红细胞抗体诱导小鼠中的红细胞轻微且短暂的消耗(血细胞比容降低约5%),可增加一定范围的循环半衰期短循环和长循环纳米颗粒制剂的使用量最多可增加32倍。用抗红细胞抗体治疗动物可显着改善CD4 +的靶向性荧光抗CD4抗体偶联的纳米粒子在体内的细胞内,磁引导的铁磁流体纳米粒子向皮下肿瘤同种异体移植物和异种移植物的体内递送以及用载有阿霉素和磁铁矿的磁引导脂质体或经临床批准的'隐身术治疗皮下肿瘤同种异体移植物阿霉素脂质体。单核吞噬细胞系统的瞬时和部分阻断可增强多种纳米颗粒药物的性能。

更新日期:2020-07-06
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