Stealthiness and Hematocompatibility of Gold Nanoparticles with Pre-Formed Protein Corona.

Studies have established that a serum protein corona pre-formed around gold nanorods (NRs) could be exploited for loading photosensitizers and chemotherapeutics to result in efficient cell kill with an extremely low dose. In this study, we further demonstrated that pre-forming a serum protein corona (PC) around citrate-capped NRs (NR-Cit) to form NR-PC conferred them stealth property and high hematocompatibility similar to the common strategy of PEGylating NRs, which would otherwise not be able to evade the immune system. Specifically, the NR-PC caused minimal complement activation with significantly lower formation of the terminal complement complex SC5b-9 measured in human serum containing NR-PC, and this resulted in low uptake by phagocytic U937 monocytes of 5.

Dynamics of Human Serum Albumin Corona Formation on Gold Nanorods with Different Surface Ligands In Silico.

The interaction between human serum albumin (HSA) and nanoparticles (NPs) to form HSA corona has widely been studied since endogenous functions of albumin are highly attractive for drug delivery. However, a full understanding of the molecular dynamics and factors behind the formation of HSA corona, including interactions between HSA and different surface ligands and between neighboring HSA molecules, resulting in conformational change of HSA is presently lacking. Here, we assembled 14 HSA molecules around gold nanorods (AuNRs) with different surface chemistries (bare gold surface, cetyltrimethylammonium bromide (CTAB), polystyrene sulfonate (PSS), and polydiallyldimethylammonium chloride (PDADMAC)) in silico and examined the dynamics of HSA corona formation using coarse-grained molecular dynamics for 300 ns of simulation.

Polyelectrolyte stiffness on gold nanorods mediates cell membrane damage.

Charge and surface chemistry of gold nanorods (AuNRs) are often considered the predictive factors for cell membrane damage. Unfortunately, extensive research on AuNR passivated with polyelectrolyte (PE) ligand shell (AuNR-PE) has hitherto left a vital knowledge gap between the mechanical stability of the ligand shell and the cytotoxicity of AuNR-PEs. Here, the agreement between unbiased coarse-grained molecular dynamics (CGMD) simulation and empirical outcomes on hemolysis of red blood cells by AuNR-PEs demonstrates for the first time, a direct impact of the mechanical stability of the PE shell passivating the AuNRs on the lipid membrane rupture.

Sequestration of Cetyltrimethylammonium Bromide on Gold Nanorods by Human Serum Albumin Causes Its Conformation Change.

Serum albumin could potentially be exploited to form a protein corona on gold nanorods (AuNRs) for drug delivery because of its endogenous functionality as a small molecule carrier. However, the cetyltrimethylammonium bromide (CTAB) surfactant, which is a synthesis byproduct passivating AuNRs to confer colloidal stability, could also cause its conformational change upon interaction with serum albumin during the process of corona formation, thus altering its biological functions. Unfortunately, a clear understanding of how exactly human serum albumin (HSA) would change its conformation as it interacts with AuNR-CTAB is presently lacking.

Protein Corona Formed from Different Blood Plasma Proteins Affects the Colloidal Stability of Nanoparticles Differently.

Significant progress in the characterization of protein corona has been made. However, insights on how the corona affects the aggregation of nanoparticles (NPs) and consequent biological identity are still lacking. Here, we examined how the corona formed from four major serum proteins, immunoglobulin G (IgG), fibrinogen (FBG), apolipoprotein A1 (ApoA1), and human serum albumin (HSA), over a range of concentrations affects the aggregation of gold NPs (AuNPs).

Quantifying Vascular Distribution and Adhesion of Nanoparticles with Protein Corona in Microflow.

The protein corona has emerged as an important determinant of biological response in nanoparticle (NP) drug delivery. However, there is presently no reported study on how the protein corona affects the behavior of NPs in microflow and its subsequent interactions with the vascular endothelium, which could affect their delivery to the target tumor site regardless of its targeting mechanism. Furthermore, a consensus on the role of physical and surface characteristics of NPs in affecting the margination of NPs is lacking due to different methods of quantifying margination.