Biomimetic Protein Materials for Adjuvant-Free Dermal Penetration.

用于无佐剂真皮渗透的仿生蛋白材料

Marianna Favaro, Eric Voltà-Durán, Julieta Sánchez, Elvira Escribano-Ferrer, Vanesa Huaca, Eva Miranda-Tovar, Ugutz Unzueta, Eloi Parladé, Esther Vázquez, Ramon Mangues, Antonio Villaverde, Isolda Casanova (2026) Biomimetic Protein Materials for Adjuvant-Free Dermal Penetration. ACS Mater Lett (IF: 8.7) 2 区 8(4) 1045-1054

Abstract

The effective dermal delivery of functional proteins could substantially improve therapeutic options for common skin disorders, in which current lipid-based or invasive strategies face efficacy and safety limitations. We report a biomimetic protein depot platform based on granular, nontoxic amyloids generated through Zn-mediated coordination of hexahistidine-tagged proteins. Functionalization of these materials with either the cell-penetrating peptide R9 or the tight junction modulator c-CPE, the C-terminal region of the Clostridium perfringens enterotoxin, enabled a systematic evaluation of transdermal penetration in mouse models. Whereas plain and R9-functionalized granules showed restricted permeation, c-CPE-functionalized granules achieved consistent distribution through the dermis into the hypodermal layers. These findings establish self-assembled protein amyloids as a promising and adaptable class of biomaterials for dermal protein delivery. Also, the ability of c-CPE to enhance permeability without auxiliary adjuvants, lipids, or invasive methods highlights the translational potential of this system for clinically applicable, noninvasive management of cutaneous conditions.© 2026 The Authors. Published by American Chemical Society.

功能性蛋白的有效真皮递送有望显著改善常见皮肤疾病的治疗选择，而目前基于脂质或侵入性疗法的治疗方法在疗效和安全性方面存在局限性。我们报道了一种基于颗粒状无毒淀粉样蛋白的仿生蛋白储存平台，该淀粉样蛋白是通过锌介导的六组氨酸标签蛋白配位生成的。将这些材料分别用细胞穿透肽R9或紧密连接调节剂c-CPE（产气荚膜梭菌肠毒素的C端区域）进行功能化修饰，从而能够在小鼠模型中系统地评估其经皮渗透性。结果表明，未修饰的颗粒和R9功能化的颗粒渗透性受限，而c-CPE功能化的颗粒则能够均匀地分布于真皮层并进入皮下组织。这些发现表明，自组装蛋白淀粉样蛋白是一种很有前景且适应性强的真皮蛋白递送生物材料。此外，c-CPE无需辅助佐剂、脂质或侵入性方法即可增强渗透性，这凸显了该系统在临床应用、无创治疗皮肤疾病方面的转化潜力。© 2026 作者。由美国化学学会出版。