Elongated PEO-based nanoparticles bind the high-density lipoprotein (HDL) receptor scavenger receptor class B I (SR-BI)
Elongated PEO-based nanoparticles bind the high-density lipoprotein (HDL) receptor scavenger receptor class B I (SR-BI)
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DOI：
10.1016/j.jconrel.2021.07.045
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发表时间：
2021-08-06
影响因子：
10.8
通讯作者：
Dalhaimer，Paul
中科院分区：
文献类型：
--
作者：
Raith，Mitch;Kauffman，Sarah J.;Dalhaimer，Paul
用纳米颗粒（NP）靶向细胞表面受体是纳米医学的一个重要方面。在这里，我们表明，软，灵活，细长的纳米粒子与聚环氧乙烷（PEO）的外部和聚丁二烯（PBD）的内部- PEO-PBD filomicelles -直接与主要的高密度脂蛋白（HDL）受体和SARS-CoV-2摄取因子，SR-BI相互作用。与PEO-PBD球相比，丝状胶束与重构SR-BI的相互作用强约6倍。HDL和脂质转运抑制剂BLT-1均阻断巨噬细胞和Idla 7细胞对丝状胶束的摄取，后者组成型表达SR-BI（Idla 7-SR-BI）。将HDL和丝状胶束共注射到野生型小鼠中减少了肝脏中的丝状胶束信号并增加了丝状胶束血浆水平。SCARB 1 −/−小鼠也是如此。SR-BI结合之后是用于丝胶束巨噬细胞进入的吞噬作用，但进入Idla 7-SR-BI细胞仅需要SR-BI。在上述实验中，PEO-PBD球与SR-BI没有强烈的相互作用。结果表明，细长的基于PEO的NPs可以通过细胞表面SR-BI受体之间的协同作用结合细胞。
Targeting cell-surface receptors with nanoparticles (NPs) is a crucial aspect of nanomedicine. Here, we show that soft, flexible, elongated NPs with poly-ethylene-oxide (PEO) exteriors and poly-butadiene (PBD) interiors – PEO-PBD filomicelles - interact directly with the major high-density lipoprotein (HDL) receptor and SARS-CoV-2 uptake factor, SR-BI. Filomicelles have a ~ 6-fold stronger interaction with reconstituted SR-BI than PEO-PBD spheres. HDL, and the lipid transport inhibitor, BLT-1, both block the uptake of filomicelles by macrophages and Idla7 cells, the latter are constitutively expressing SR-BI (Idla7-SR-BI). Co-injections of HDL and filomicelles into wild-type mice reduced filomicelle signal in the liver and increased filomicelle plasma levels. The same was true withSCARB1−/−mice. SR-BI binding is followed by phagocytosis for filomicelle macrophage entry, but only SR-BI is needed for entry into Idla7-SR-BI cells. PEO-PBD spheres did not interact strongly with SR-BI in the above experiments. The results show elongated PEO-based NPs can bind cellsviacooperativity among SR-BI receptors on cell surfaces.