Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies

Abstract

Recent advances in wet chemical synthesis and biomolecular functionalization of gold nanoparticles have led to a dramatic expansion of their potential biomedical applications, including biosensorics, bioimaging, photothermal therapy, and targeted drug delivery. As the range of gold nanoparticle types and their applications continues to increase, human safety concerns are gaining attention, which makes it necessary to better understand the potential toxicity hazards of these novel materials. Whereas about 80 reports on the in vivo biodistribution and in vitro cell toxicity of gold nanoparticles are available in the literature, there is lack of correlation between both fields and there is no clear understanding of intrinsic nanoparticle effects. At present, the major obstacle is the significant discrepancy in experimental conditions under which biodistribution and toxicity effects have been evaluated. This critical review presents a detailed analysis of data on the in vitro and in vivo biodistribution and toxicity of most popular gold nanoparticles, including atomic clusters and colloidal particles of diameters from 1 to 200 nm, gold nanoshells, nanorods, and nanowires. Emphasis is placed on the systematization of data over particle types and parameters, particle surface functionalization, animal and cell models, organs examined, doses applied, the type of particle administration and the time of examination, assays for evaluating gold particle toxicity, and methods for determining the gold concentration in organs and distribution of particles over cells. On the basis of a critical analysis of data, we arrive at some general conclusions on key nanoparticle parameters, methods of particle surface modification, and doses administered that determine the type and kinetics of biodistribution and toxicity at cellular and organismal levels (197 references).

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…Apoptosis trigged by a chemotherapeutic agent is enhanced when a drug efflux pump (e.g., P-gp) or prosurvival protein (e.g., Bcl-2) is inhibited by RNAi. plasmon resonance (SPR) at the NIR region [209][210][211][212], with high biocompatibility and facile surface functionalization [213,214]. Combined photothermal and chemotherapy via ablation of hepatocellular carcinomas both in vivo and in vitro was explored using gold nanoshells (AuNSs) [215,216] consisting of a mesoporous silica nanorattle core and a thin outer gold shell [215].…”

Controllable Cobalt Oxide/Au Hierarchically Nanostructured Electrode for Nonenzymatic Glucose Sensing

“…Gold nanostructures are often used to overcome the limitations found with standard contrast agents [359][360][361][362]. In addition to their biocompatibility, Au nanoparticles have longer in vivo circulation times during the imaging process and in some cases faster elimination time post-procedure [356,[363][364][365].…”

High-content analysis for drug delivery and nanoparticle applications

“…Still, potential toxicity of Au-NP remains a topic of debate because, although Au has been used as an antirheumatoid arthritis therapeutic for decades and is widely thought to have minimal toxicology, it now features in NP formats being developed for oral insulin [67] and injectable targeted anticancer payloads [68]. Size, shape, and functionalization might alter in vivo biodistribution and this has toxicity implications even for wellestablished materials [69].…”

“…Still, potential toxicity of Au-NP remains a topic of debate because, although Au has been used as an antirheumatoid arthritis therapeutic for decades and is widely thought to have minimal toxicology, it now features in NP formats being developed for oral insulin [67] and injectable targeted anticancer payloads [68]. Size, shape, and functionalization might alter in vivo biodistribution and this has toxicity implications even for wellestablished materials [69].From the above discussion, the selection of cell type and the state of cell differentiation are crucial decisions in HCA study designs. NP toxicology studies for systemic delivery applications require HepG2 cells, whereas human lung and skin fibroblast cell lines are more appropriate for aerosols and skin exposure, respectively.…”