Abstract
Engineered nanoparticles are utilized as drug delivery carriers in modern medicine due to their high surface area and tailorable surface functionality. After in vivo administration, nanoparticles distribute and interact with biomolecules, such as polar proteins in serum, lipid membranes in cells, and high ionic conditions during digestion. Electrostatic forces and steric hindrances in a nanoparticle population are disturbed and particles agglomerate in biological fluids. Little is known about the stability of nanoparticles in relation to particle surface charge. Here, we compared three different surface-stabilized silver nanoparticles (50 nm) for intracellular agglomeration in human hepatocellular carcinoma cells (HepG2). Nanoparticles stabilized with branched polyethyleneimine conferred a positive surface charge, particles stabilized with lipoic acid conferred a negative surface charge, and particles stabilized with polyethylene glycol conferred a neutral surface charge. Particles were incubated in fetal bovine serum, simulated lung surfactant fluid, and simulated stomach digestion fluid. Each nanoparticle system was characterized via microscopic (transmission electron, fluorescence, and enhanced darkfield) and spectroscopic (hyperspectral, dynamic light scattering, and ultraviolet-visible absorption) techniques. Results showed that nanoparticle transformation included cellular internalization, agglomeration, and degradation and that these changes were dependent upon surface charge and incubation matrix. Hyperspectral analyses showed that positively charged silver nanoparticles red-shifted in spectral analysis after transformations, whereas negatively charged silver nanoparticles blue-shifted. Neutrally charged silver nanoparticles did not demonstrate significant spectral shifts. Spectral shifting indicates de-stabilization in particle suspension, which directly affects agglomeration intracellularly. These characteristics are translatable to critical quality attributes and can be exploited when developing nano-carriers for nanomedicine.
Highlights
Silver nanoparticles (AgNPs), first used in consumer health-related products in the late 1800s, continue to be incorporated into modern medicine due to their unique properties [1]. Properties such as small size and large surface area, relative low toxicity, and stability while in suspension are useful in drug delivery carriers (DDCs) [2,3]
Given that nanoparticles are currently used in drug delivery systems, the goal of this study was to compare the effects of surface stabilizing agents, and induced surface charge, on nanoparticle physiologically relevant transformation, including cellular internalization, agglomeration, and degradation
We transformed three different AgNPs (50 nm); nanoparticles stabilized with branched polyethyleneimine conferred a positive surface charge, nanoparticles stabilized with lipoic acid conferred a negative surface charge, and nanoparticles stabilized with polyethylene glycol (PEG) conferred a neutral surface charge
Summary
Silver nanoparticles (AgNPs), first used in consumer health-related products in the late 1800s, continue to be incorporated into modern medicine due to their unique properties [1] Properties such as small size and large surface area, relative low toxicity, and stability while in suspension are useful in drug delivery carriers (DDCs) [2,3]. Given that nanoparticles are currently used in drug delivery systems, the goal of this study was to compare the effects of surface stabilizing agents, and induced surface charge, on nanoparticle physiologically relevant transformation, including cellular internalization, agglomeration, and degradation. This work outlines a reproducible methodology that can be repeated when characterizing nano-enabled drug product transformations after administration These characteristics are translatable to critical quality attributes and can be exploited to develop complex in vitro, in vivo, or in silico models for nanomedicine and associated risk analyses
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