The Nano-War Against Complement Proteins.

The Nano-War Against Complement Proteins.
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DOI:
10.1208/s12248-021-00630-9
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发表时间:
2021-09-10
期刊:
The AAPS journal
影响因子:
--
通讯作者:
Brenner JS
Brenner JS
中科院分区:
其他
文献类型:
--
作者:
Wang Z;Brenner JS

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靶向药物递送和纳米医学具有将药物单独递送到目标器官或细胞类型的潜在前景,从而减少脱靶副作用并提高疗效。然而,纳米级药物载体在实现这一目标的过程中面临着一些障碍,其中最令人生畏的是补体级联。补体蛋白,尤其是C3,不仅调理它们所包含的微生物,还调理纳米载体。这导致了多种问题,包括标记纳米载体以供白细胞清除,可能污染纳米载体上的靶向部分,以及释放毒素,产生有害的局部和全身效应。本文综述了补体如何实现对纳米药物的阻断,哪些纳米载体材料的特性最好地避免了补体,以及当前和未来控制补体以释放纳米药物潜力的策略。
Targeted drug delivery and nanomedicine hold the potential promise of delivering drugs solely to target organs or cell types, thus decreasing off-target side effects and improving efficacy. However, nano-scale drug carriers face several barriers to this goal, with one of the most formidable being the complement cascade. Complement proteins, especially C3, opsonize not just the microbes they evolved to contain, but also nanocarriers. This results in multiple problems, including marking the nanocarriers for clearance by leukocytes, likely fouling of the targeting moieties on nanocarriers, and release of toxins which produce deleterious local and systemic effects. Here, we review how complement achieves its blockade of nanomedicine, which nanocarrier materials properties best avoid complement, and current and future strategies to control complement to unleash nanomedicine’s potential.
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