Mass Spectrometry-Based Top-Down Proteomics in Nanomedicine: Proteoform-Specific Measurement of Protein Corona,ACS Nano

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Mass Spectrometry-Based Top-Down Proteomics in Nanomedicine: Proteoform-Specific Measurement of Protein Corona
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-14 , DOI: 10.1021/acsnano.4c04675
Seyed Amirhossein Sadeghi ₁ , Ali Akbar Ashkarran ₂ , Qianyi Wang ₁ , Guijie Zhu ₁ , Morteza Mahmoudi ₂ , Liangliang Sun ₁

Affiliation

Conventional mass spectrometry (MS)-based bottom-up proteomics (BUP) analysis of the protein corona [i.e., an evolving layer of biomolecules, mostly proteins, formed on the surface of nanoparticles (NPs) during their interactions with biomolecular fluids] enabled the nanomedicine community to partly identify the biological identity of NPs. Such an approach, however, fails to pinpoint the specific proteoforms─distinct molecular variants of proteins in the protein corona. The proteoform-level information could potentially advance the prediction of the biological fate and pharmacokinetics of nanomedicines. Recognizing this limitation, this study pioneers a robust and reproducible MS-based top-down proteomics (TDP) technique for characterizing proteoforms in the protein corona. Our TDP approach has successfully identified about 900 proteoforms in the protein corona of polystyrene NPs, ranging from 2 to 70 kDa, revealing proteoforms of 48 protein biomarkers with combinations of post-translational modifications, signal peptide cleavages, and/or truncations─details that BUP could not fully discern. This advancement in MS-based TDP offers a more advanced approach to characterize NP protein coronas, deepening our understanding of NPs’ biological identities. We, therefore, propose using both TDP and BUP strategies to obtain more comprehensive information about the protein corona, which, in turn, can further enhance the diagnostic and therapeutic efficacy of nanomedicine technologies.

中文翻译：

纳米医学中基于质谱的自上而下的蛋白质组学：蛋白质冠的蛋白质特异性测量

传统的基于质谱 (MS) 的自下而上蛋白质组学 (BUP) 分析蛋白冠 [即，在纳米粒子 (NP) 与生物分子流体相互作用过程中在纳米颗粒 (NP) 表面形成的不断演化的生物分子层，主要是蛋白质]纳米医学界部分鉴定纳米颗粒的生物学特性。然而，这种方法无法精确定位特定的蛋白质形式——蛋白质冠中蛋白质的独特分子变体。蛋白质形式水平的信息可能会促进纳米药物的生物命运和药代动力学的预测。认识到这一局限性，本研究开创了一种稳健且可重复的基于 MS 的自上而下蛋白质组学 (TDP) 技术，用于表征蛋白质冠中的蛋白质形式。我们的 TDP 方法已成功鉴定了聚苯乙烯纳米颗粒蛋白冠中的约 900 种蛋白质形式，范围从 2 到 70 kDa，揭示了 48 种蛋白质生物标志物的蛋白质形式，并结合了翻译后修饰、信号肽裂解和/或截短 —BUP 的详细信息无法完全辨别。基于 MS 的 TDP 的这一进步提供了一种更先进的方法来表征 NP 蛋白冠，加深了我们对 NP 生物学特性的理解。因此，我们建议同时使用TDP和BUP策略来获得有关蛋白冠的更全面的信息，这反过来又可以进一步提高纳米医学技术的诊断和治疗效果。

更新日期：2024-09-14

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