Interaction of Metallic Nanoparticles With Biomimetic Lipid Liquid Crystalline Cubic Interfaces

Abstract

In the past decades, events occurring at the nano-bio interface (i.e., where engineered nanoparticles (NPs) meet biological interfaces such as biomembranes) have been intensively investigated, to address the cytotoxicity of nanomaterials and boost their clinical translation. In this field, lamellar synthetic model membranes have been instrumental to disentangle non-specific interactions between NPs and planar biological interfaces. Much less is known on nano-biointeractions occurring at highly curved biological interfaces, such as cubic membranes. These non-lamellar architectures play a crucial -but far from understood-role in several biological processes and occur in cells as a defence mechanism against bacterial and viral pathologies, including coronaviruses infections. Despite its relevance, the interaction of cubic membranes with nano-sized objects (such as viral pathogens, biological macromolecules and synthetic NPs) remains largely unexplored to date. Here, we address the interaction of model lipid cubic phase membranes with two prototypical classes of NPs for Nanomedicine, i.e., gold (AuNPs) and silver NPs (AgNPs). To this purpose, we challenged lipid cubic phase membranes, either in the form of dispersed nanoparticles (i.e., cubosomes) or solid-supported layers of nanometric thickness, with citrate-stabilized AuNPs and AgNPs and monitored the interaction combining bulk techniques (UV-visible spectroscopy, Light and Synchrotron Small-Angle X-ray Scattering) with surface methods (Quartz Crystal Microbalance and Confocal Laser Scanning Microscopy). We show that the composition of the metal core of NPs (i.e., Au vs Ag) modulates their adsorption and self-assembly at cubic interfaces, leading to an extensive membrane-induced clustering of AuNPs, while only to a mild adsorption of isolated AgNPs. Such differences mirror opposite effects at the membrane level, where AuNPs induce lipid extraction followed by a fast disruption of the cubic assembly, while AgNPs do not affect the membrane morphology. Finally, we propose an interaction mechanism accounting for the different behaviour of AuNPs and AgNPs at the cubic interface, highlighting a prominent role of NPs’ composition and surface chemistry in the overall interaction mechanism.

Biomimetic Nanomaterials: Diversity, Technology, and Biomedical Applications

“…Finally, by analyzing the most recent literary sources, it was possible to list the main challenges that stand in the way of the development of BNM technology: (i) there remains much room for the improvement of BNMs in terms of their stability and biocompatibility since BNMs have been used only in animal studies, but they have not been widely used in clinical practice [ 22 ]; (ii) understanding the energetic contributions that rule interactions at the nano–bio interface (i.e., where NPs meet biological barriers, specifically cell membranes) is very complex due to the high compositional heterogeneity of biomembranes and the intrinsic variability of the biological environment [ 34 ]; (iii) the clinical application of BNMs encounters complex fabrication processes, unsuitable large-scale production, low yields, and difficult preservation [ 24 ]; (iv) the utilization of biosynthesis (e.g., engineered bacteria) requires scaled-up manufacturing, dose determination, and potential biosafety studies [ 23 ]; (v) the processing of biomaterials (e.g., bioprinting) that incorporate living cells is still very challenging, especially considering that the production of mechanically rigid and insoluble substrates usually requires nonbiocompatible processes, such as chemical cross-linking or sintering [ 65 ].…”

“…The new, proposed biomimetic methods for obtaining Au NPs and Ag NPs include the use of “cubosomes”, model cubic nanostructures based on lipid membranes. Such BNMs are obtained through incubating preformed Au or Ag NPs with cubosomes in an aqueous solution [ 34 ] ( Figure 9 ). The purpose of BNMs based on cubosomes is the targeted delivery of drugs.…”

“… Classification of biomimetic nanomaterials (BNMs) based on the literature data, including information on biomimetic structure [ 16 , 34 , 35 , 36 , 37 , 38 ], biomimetic synthesis [ 32 , 39 , 40 , 41 , 42 , 43 ], biogenic components [ 31 , 33 , 44 , 45 , 46 , 47 ], magnetic BNMs [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ], metal and metal oxide BNMs [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ], organic, ceramic and hybrid BNMs [ 62 , 63 , 64 , 65 , 66 , 67 ]. …”

“… Schematic representation of the mechanism and final outcomes of the interaction of Au NPs and Ag NPs with a water dispersion of cubosomes and solid-supported films of cubosomes. (Reprinted from [ 34 ], license CC BY 4.0.) …”

“…Due to the wide variety of proposed structures and compositions of BNMs, the use of magnetic, metal, and metal oxide materials, as well as organic, ceramic, and hybrid (multicomponent) structural elements, are considered separately. The proposed classification with some examples from the literature, including information on biomimetic structure [ 16 , 34 , 35 , 36 , 37 , 38 ], biomimetic synthesis [ 32 , 39 , 40 , 41 , 42 , 43 ], biogenic components [ 31 , 33 , 44 , 45 , 46 , 47 ], magnetic BNMs [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ], metal and metal oxide BNMs [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ], organic, ceramic and hybrid BNMs [ 62 , 63 , 64 , 65 , 66 , 67 ], is shown in Figure 2 .…”