Morillas-Becerril Lucía, Franco-Ulloa Sebastian, Fortunati Ilaria, Marotta Roberto, Sun Xiaohuan, Zanoni Giordano, De Vivo Marco, Mancin Fabrizio
Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, Padova, Italy.
Laboratory of Molecular Modeling and Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, Genoa, Italy.
Commun Chem. 2021 Jun 18;4(1):93. doi: 10.1038/s42004-021-00526-x.
Understanding and controlling the interaction between nanoparticles and biological entities is fundamental to the development of nanomedicine applications. In particular, the possibility to realize nanoparticles capable of directly targeting neutral lipid membranes would be advantageous to numerous applications aiming at delivering nanoparticles and their cargos into cells and biological vesicles. Here, we use experimental and computational methodologies to analyze the interaction between liposomes and gold nanoparticles (AuNPs) featuring cationic headgroups in their protecting monolayer. We find that in contrast to nanoparticles decorated with other positively charged headgroups, guanidinium-coated AuNPs can bind to neutral phosphatidylcholine liposomes, inducing nondisruptive membrane permeabilization. Atomistic molecular simulations reveal that this ability is due to the multivalent H-bonding interaction between the phosphate residues of the liposome's phospholipids and the guanidinium groups. Our results demonstrate that the peculiar properties of arginine magic, an effect responsible for the membranotropic properties of some naturally occurring peptides, are also displayed by guanidinium-bearing functionalized AuNPs.
理解和控制纳米颗粒与生物实体之间的相互作用是纳米医学应用发展的基础。特别是，实现能够直接靶向中性脂质膜的纳米颗粒的可能性，对于众多旨在将纳米颗粒及其所载物质递送至细胞和生物小泡的应用将是有利的。在此，我们使用实验和计算方法来分析脂质体与在其保护单层中具有阳离子头基的金纳米颗粒（AuNP）之间的相互作用。我们发现，与用其他带正电荷的头基修饰的纳米颗粒不同，胍基包覆的AuNP可以与中性磷脂酰胆碱脂质体结合，诱导非破坏性的膜通透性。原子分子模拟表明，这种能力归因于脂质体磷脂的磷酸残基与胍基之间的多价氢键相互作用。我们的结果表明，含胍基的功能化AuNP也表现出精氨酸魔力的独特性质，这是某些天然存在的肽的膜向性性质的原因。
