了解纳米载体和血浆蛋白之间的相互作用对于控制它们的生物命运至关重要。根据报道的聚合物纳米胶囊（NC）在肿瘤药物靶向递送方面的潜力，这项工作的主要目的是研究表面化学成分如何影响其蛋白质电晕指纹。因此，我们开发了六种具有不同聚合物外壳和理化性质的 NC 原型，并量化了在人血浆中孵育时吸附的蛋白质量。使用所有理论质谱 (SWATH-MS) 的连续窗口采集并遵循有关纳米材料生物电晕实验的最低信息 (MINBE) 指南，我们确定了不同的蛋白质电晕模式。正如预期的那样，聚合物壳中聚乙二醇 (PEG) 的存在减少了蛋白质电晕，特别是免疫球蛋白的吸附。然而，通过比较不同的原型，我们得出结论，蛋白质吸附模式并不完全由 PEG 驱动。事实上，高度聚乙二醇化的原型表现出强烈的载脂蛋白 IV 吸附。另一方面，我们还观察到含有 1,2-二油酰基-3-三甲基丙烷铵 (DOTAP) 的聚合 NC 对玻连蛋白具有高吸附性，玻连蛋白是一种已知可增强肺上皮和几种癌细胞对纳米系统的摄取的蛋白质。总体而言，收集到的信息使我们能够识别出有前景的聚合NC，其具有预期的延长循环时间、增强的肿瘤靶向性、肝脏积聚以及免疫系统的优先摄取。从这个意义上说，在这项工作中进行的蛋白质电晕分析有望有助于推进新一代合理设计的纳米药物输送系统。© 2023。控释协会。

Understanding the interactions between nanocarriers and plasma proteins is essential for controlling their biological fate. Based on the reported potential of polymeric nanocapsules (NCs) for the targeted delivery of oncological drugs, the main objective of this work has been to investigate how the surface chemical composition influences their protein corona fingerprint. Thus, we developed six NC prototypes with different polymer shells and physicochemical properties and quantified the amount of protein adsorbed upon incubation in human plasma. Using sequential window acquisition of all theoretical mass spectra (SWATH-MS) and following the Minimum Information about Nanomaterial Biocorona Experiments (MINBE) guidelines, we identified different protein corona patterns. As expected, the presence of polyethylene glycol (PEG) in the polymer shell reduced the protein corona, particularly the adsorption of immunoglobulins. However, by comparing the different prototypes, we concluded that the protein adsorption pattern was not exclusively driven by PEG. In fact, a highly PEGylated prototype exhibited intense apolipoprotein IV adsorption. On the other hand, we also observed that polymeric NCs containing 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) exhibited high adsorption of vitronectin, a protein that is known for enhancing the uptake of nanosystems by lung epithelium and several cancer cells. Overall, the gathered information allowed us to identify promising polymeric NCs with an expected prolonged circulation time, enhanced tumor targeting, liver accumulation, and preferential uptake by the immune system. In this sense, the analyses of the protein corona performed along this work will hopefully contribute to advancing a new generation of rationally designed nanometric drug delivery systems.© 2023. Controlled Release Society.