<p>Size-Dependent Interactions of Lipid-Coated Gold Nanoparticles: Developing a Better Mechanistic Understanding Through Model Cell Membranes and in vivo Toxicity</p>

Abstract

Introduction: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications. Methods and Materials: Here, AuNPs of three sizes, 5 nm, 10 nm, and 20 nm, were coated with a lipid bilayer composed of sodium oleate, hydrogenated phosphatidylcholine, and hexanethiol. To understand how the physical features of AuNPs influence uptake through cellular membranes, sum frequency generation (SFG) was utilized to assess the interactions of the AuNPs with a biomimetic lipid monolayer composed of a deuterated phospholipid 1.2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC). Results and Discussion: SFG measurements showed that 5 nm and 10 nm AuNPs are able to phase into the lipid monolayer with very little energetic cost, whereas, the 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs. Toxicity of the AuNPs were assessed in vivo to determine how AuNP curvature and uptake influence cell health. In contrast, in vivo toxicity tested in embryonic zebrafish showed rapid toxicity of the 5 nm AuNPs, with significant 24 hpf mortality occurring at concentrations ≥20 mg/L, whereas the 10 nm and 20 nm AuNPs showed no significant mortality throughout the five-day experiment. Conclusion: By combining information from membrane models using SFG spectroscopy with in vivo toxicity studies, a better mechanistic understanding of how nanoparticles (NPs) interact with membranes is developed to understand how the physiochemical features of AuNPs drive nanoparticle-membrane interactions, cellular uptake, and toxicity.

Silver Nanoparticles Stable to Oxidation and Silver Ion Release Show Size-Dependent Toxicity In Vivo

“…When comparing spherical hybrid-lipid-coated AgNPs (10 nm) to triangular-shaped (32 nm) particles, the spherical hybrid lipid-coated AgNPs were determined to be more toxic than triangular-shaped AgNPs, suggesting that the size and shape of the AgNPs contribute to toxicity in embryonic zebrafish (Danio rerio) [72]. Studies with similar hybrid lipid-coated gold nanoparticles (AuNPs) of 5, 10, and 20 nm in zebrafish embryos showed rapid toxicity with 5 nm AuNPs and significant mortality occurring at concentrations ≥20 mg/L compared to the 10 nm and 20 nm AuNPs, which showed no significant mortality throughout the 5-day experiment [73]. Using model membranes and sum-frequency gain (SFG) spectroscopy, Engstrom et al showed that 5 nm and 10 nm AuNPs can phase into the lipid monolayer with very little energetic cost; whereas 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs [73].…”

“…Studies with similar hybrid lipid-coated gold nanoparticles (AuNPs) of 5, 10, and 20 nm in zebrafish embryos showed rapid toxicity with 5 nm AuNPs and significant mortality occurring at concentrations ≥20 mg/L compared to the 10 nm and 20 nm AuNPs, which showed no significant mortality throughout the 5-day experiment [73]. Using model membranes and sum-frequency gain (SFG) spectroscopy, Engstrom et al showed that 5 nm and 10 nm AuNPs can phase into the lipid monolayer with very little energetic cost; whereas 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs [73]. Because the 5 nm have a lower energy barrier to cross the membrane, their uptake is greater and could lead to the increased toxicity observed [73].…”

“…Using model membranes and sum-frequency gain (SFG) spectroscopy, Engstrom et al showed that 5 nm and 10 nm AuNPs can phase into the lipid monolayer with very little energetic cost; whereas 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs [73]. Because the 5 nm have a lower energy barrier to cross the membrane, their uptake is greater and could lead to the increased toxicity observed [73]. While the combined use of SFG spectroscopy and in vivo toxicity assays can explain the structure-property relationships, understanding the effect of a range of sizes of AgNPs of one shape is yet to be determined.…”

Effect of Particle size on&nbsp;Biomedical Behaviors&nbsp;of Sub-micron Silk Fibroin

“…Taking this feature, smaller sized contrast agents excreted through the kidney are suitable as functional renal contrast agents, while larger sized are found better suited for blood and lymphatic imaging. The similar phenomenon of size effect also exist in gold nanoparticles (11) and iron oxide (12). Like those nano and sub-micron materials, particle size of silk broin will potentially in uence its blood clearance, metabolic pathways, and metabolic rate, especially when silk broin takes spherical shape in biomedical applications.…”

Engineering the Interface between Inorganic Nanoparticles and Biological Systems through Ligand Design

“…Inorganic nanoparticles can be engineered to possess useful physiochemical properties for use in applications including biomedicine and diagnostics [ 1 , 2 , 3 , 4 , 5 , 6 ]. While shape [ 7 ] and size [ 8 ] both play critical roles in defining nanoparticle properties, surface chemistry is likewise crucial for function and colloidal stability [ 9 , 10 ]. The nanoparticle surface interfaces with the external environment, and appropriately engineered surfaces can be used to regulate interactions between nanoparticles and biomolecules [ 11 ] including peptides [ 12 ], proteins [ 13 ] and nucleic acids [ 14 ].…”