Protein adsorption onto nanomaterials often results in denaturation and loss of bioactivity. Controlling the adsorption process to maintain the protein structure and function has potential for a range of applications. Here we report that self-assembled poly(propylene sulfone) (PPSU) nanoparticles support the controlled formation of multicomponent enzyme and antibody coatings and maintain their bioactivity. Simulations indicate that hydrophobic patches on protein surfaces induce a site-specific dipole relaxation of PPSU assemblies to non-covalently anchor the proteins without disrupting the protein hydrogen bonding or structure. As a proof of concept, a nanotherapy employing multiple mast-cell-targeted antibodies for preventing anaphylaxis is demonstrated in a humanized mouse model. PPSU nanoparticles displaying an optimized ratio of co-adsorbed anti-Siglec-6 and anti-FcεRIα antibodies effectively inhibit mast cell activation and degranulation, preventing anaphylaxis. Protein immobilization on PPSU surfaces provides a simple and rapid platform for the development of targeted protein nanomedicines.

蛋白质吸附到纳米材料上通常会导致变性和生物活性丧失。控制吸附过程以维持蛋白质结构和功能具有广泛的应用潜力。在这里，我们报告自组装聚（丙烯砜）（PPSU）纳米粒子支持多组分酶和抗体涂层的受控形成并保持其生物活性。模拟表明，蛋白质表面上的疏水斑块会诱导 PPSU 组装体发生位点特异性偶极弛豫，从而非共价锚定蛋白质，而不会破坏蛋白质氢键或结构。作为概念证明，在人源化小鼠模型中展示了一种采用多种肥大细胞靶向抗体来预防过敏反应的纳米疗法。PPSU 纳米粒子显示出共吸附的抗 Siglec-6 和抗 FcεRIα 抗体的优化比例，可有效抑制肥大细胞活化和脱粒，防止过敏反应。PPSU 表面上的蛋白质固定化为靶向蛋白质纳米药物的开发提供了简单而快速的平台。