The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on nanocarriers may provide an alternative impetus for specific drug delivery. Herein, we explore the role of glycosylated polyhydroxy polymer-modified nanovesicles (CP-LVs) with different amino/hydroxyl ratios in protein corona formation and evolution. CP-LVs with an amino/hydroxyl ratio of approximately 0.4 (CP₁-LVs) are found to efficiently suppress immunoglobulin adsorption in blood and livers, resulting in prolonged circulation. Moreover, CP₁-LVs adsorb abundant tumor distinctive proteins, such as CD44 and osteopontin in tumor interstitial fluids, mediating selective tumor cell internalization. The proteins corona transformation specific to the environment appears to be affected by the electrostatic interaction between CP-LVs and proteins with diverse isoelectric points. Benefiting from surface modification-mediated protein corona regulation, paclitaxel-loaded CP₁-LVs demonstrate superior antitumor efficacy to PEGylated liposomes. Our work offers a perspective on rational surface-design of nanocarriers to modulate the protein corona formation for efficient drug delivery.

研究表明，纳米载体上形成的动态蛋白质冠会强烈影响其体内行为。精确操纵纳米载体上蛋白冠的形成可能为特定药物输送提供另一种动力。在此，我们探讨了具有不同氨基/羟基比例的糖基化多羟基聚合物修饰的纳米囊泡（CP-LV）在蛋白质冠形成和进化中的作用。氨基/羟基比约为 0.4 的 CP-LV（CP ₁ -LV）被发现可有效抑制血液和肝脏中的免疫球蛋白吸附，从而延长循环时间。此外，CP ₁ -LVs 吸附丰富的肿瘤独特蛋白，例如肿瘤间质液中的 CD44 和骨桥蛋白，介导选择性肿瘤细胞内化。特定于环境的蛋白质电晕转化似乎受到 CP-LV 和具有不同等电点的蛋白质之间的静电相互作用的影响。受益于表面修饰介导的蛋白质电晕调节，负载紫杉醇的 CP ₁ -LV 表现出优于聚乙二醇化脂质体的抗肿瘤功效。我们的工作为纳米载体的合理表面设计提供了视角，以调节蛋白质电晕的形成以实现有效的药物输送。