Silver Nanoparticles Agglomerate Intracellularly Depending on the Stabilizing Agent: Implications for Nanomedicine Efficacy

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.

Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles

“…1 , silver content increased > 7 and > 5 times the control level in livers treated with non-coated and coated AgNPs, respectively. The results related to AgNPs penetration into hepatocytes are in agreement with other studies in vivo and in vitro 70 – 72 . This cellular internalization has been also reported for other metal/chitosan/curcumin nano systems.…”

“…in the cytoplasm, curcumin molecules will be released from the biodegradable chitosan coat and interacts with the intracellular salty conditions. Alternatively, nanoparticles remain trapped in lysosomes and endosomes 75 , where they are exposed to high ionic conditions during digestion 72 . These lysosomal digestive conditions release curcumin from chitosan coat into the cytosol.…”

Silver Nanoparticles as Carriers of Anticancer Drugs for Efficient Target Treatment of Cancer Cells

“…Regarding the latter advantage, Biswas et al [44] synthesized valsartan loaded mesoporous silica nanoparticles which showed to be capable of improving the oral bioavailability of the drug. Furthermore, a negative surface charge is associated with a rapid removal of NPs from the blood compared to the existence of a neutral charge [45].…”

“…The modification of the surface of nanoparticles is of great relevance, since, in addition to decreasing the toxicity of the initial stabilizing agents and AgNPs, it also prevents their aggregation and improves the ability to target specific cells, namely cancer cells [45]. Accordingly with Gali-Muhtasib et al [5], an efficient anticancer nanocarrier must meet some requirements: (i) affinity for the anticancer drug, allowing its conjugation; (ii) exclusive release of the drug at the target site, thus presenting specificity for the tumor; (iii) the nanoparticle-anticancer drug complex must be stable in the serum; and (iv) the nanoparticles must be degraded in a way that is safe for the living organism.…”

Solid lipid nanoparticle delivery of rhynchophylline enhanced the efficiency of allergic asthma treatment via the upregulation of suppressor of cytokine signaling 1 by repressing the p38 signaling pathway

“…The mean particle size of Rhy-SLNs was found to be 62.06 ± 1.62 nm with a polymer dispersity index of 0.25 ± 0.01. It has been reported that the surface charge of nanoparticles could affect the stability of the nanoparticle [ 39 ]. The results in this study demonstrated that the zeta potential value of Rhy-SLNs was obtained as −6.53 ± 0.04 mV, which might prevent nanoparticle aggregation and keep their stability.…”