Zwitterionic peptides: Tunable next-generation stealth nanoparticle modifications
Zwitterionic peptides: Tunable next-generation stealth nanoparticle modifications
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DOI：
10.1016/j.bioactmat.2023.03.020
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发表时间：
2023-09-01
影响因子：
18.9
通讯作者：
Benoit，Danielle S. W.
中科院分区：
文献类型：
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作者：
Overby，Clyde;Park，Soomin;Benoit，Danielle S. W.
蛋白质对纳米颗粒 (NP) 的吸附是一个产生蛋白质冠的复杂过程，由定义 NP 体内相互作用的 NP 表面特性控制。通过表面改性控制吸附的蛋白质数量的努力已导致循环时间或生物分布的改善。尽管如此，目前尚未找到控制日冕内吸附蛋白质特性的方法。在这里，我们报告了用于纳米颗粒防污表面功能化的多种两性离子肽（ZIP）的开发和表征，这些两性离子肽对 ZIP 序列定义的蛋白质吸附曲线具有特定且可控的亲和力。通过 ZIP 缀合的 NP 的血清暴露和所得电晕的蛋白质组学分析，我们确定蛋白质吸附曲线并不取决于 ZIP 的确切组成，而是取决于沿序列的电荷序列（电荷基序）。这些发现为开发可调节的 ZIP 铺平了道路，以协调特定的 ZIP-NP 蛋白质吸附曲线作为 ZIP 电荷基序的函数，以更好地控制细胞和组织特异性和药代动力学，并为研究蛋白质电晕和生物功能之间的关系提供新工具。此外，氨基酸多样性带来的整体 ZIP 多样性可能会改善适应性免疫反应。
Adsorption of proteins to nanoparticles (NPs), a complex process that results in a protein corona, is controlled by NP surface properties that define NP interactionsin vivo. Efforts to control adsorbed protein quantity through surface modification have led to improvements in circulation time or biodistribution. Still, current approaches have yet to be identified to control adsorbed protein identities within the corona. Here, we report the development and characterization of diverse zwitterionic peptides (ZIPs) for NP anti-fouling surface functionalization with specific and controllable affinity for protein adsorption profiles defined by ZIP sequence. Through serum exposure of ZIP-conjugated NPs and proteomics analysis of the resulting corona, we determined that protein adsorption profiles depend not on the exact composition of the ZIPs but on the sequence and order of charges along the sequence (charge motif). These findings pave the way for developing tunable ZIPs to orchestrate specific ZIP-NP protein adsorption profiles as a function of ZIP charge motif to better control cell and tissue specificity and pharmacokinetics and provide new tools for investigating relationships between protein corona and biological function. Furthermore, overall ZIP diversity enabled by the diversity of amino acids may ameliorate adaptive immune responses.