Biodistribution, Clearance, and Toxicology of Polymeric Micelles Loaded with 0.9 or 5 nm Gold Nanoparticles

Abstract

Long-circulating gold nanoparticles (AuNPs) have garnered a great deal of interest as both imaging and therapeutic agents. However, their protracted elimination and long-term persistence within many organ systems remains a concern for clinical translation. To improve the excretion of long-circulating nanoparticles, we prepared ~80 nm biodegradable polymeric micelles with 0.9 nm or 5 nm AuNPs tightly packed within the hydrophobic core. These gold-loaded polymeric micelles (GPMs) were expected to allow for improved excretion of gold, compared with single large AuNPs, owing to the smaller size and larger surface-to-volume ratio of the individual AuNPs within the micelle. Following intravenous administration of GPMs, organs were harvested and examined for gold content using inductively coupled plasma optical emission spectrometry (ICP-OES) for up to 3 months post-injection. While both GPM formulations showed significant clearance of gold over time, micelles containing 0.9 nm AuNPs showed a 72% and 67% reduction in gold content in the liver and spleen, respectively, between 1 day and 3 months post-injection, compared with a 38% and 35% reduction in mice receiving 5 nm GPMs. Furthermore, feces and urine analysis revealed approximately 7.5 and 100 times more gold, respectively, in mice that received 0.9 nm GPMs one day after injection. These findings suggest that the excretion profile of inorganic nanomaterials may be improved if clusters of small inorganic materials are used in favor of single solid particles.

Biodegradable Ultrasmall‐in‐Nano Gold Architectures: Mid‐Period In Vivo Distribution and Excretion Assessment

“…The preservation of the ultrasmall HD is an important pre‐requisite to avoid long‐time persistence of noble metal nanoparticles in excretory system organs, a critical issue that has been confirmed by numerous investigations . Thus, NAs can effectively bypass the persistence concern, disassembling in potentially renal clearable building blocks.…”

“…[3,6] So far, although very few ultrasmall-in-nano organic constructs demonstrated some excretion abilities, no quantitative evaluation of metal clearance has been reported yet, nor assessment of innovative platforms such as NAs. [17][18][19] Thus, prior to further considering in vivo efficiency investigations of NAs, a comprehensive in-depth knowledge of metal excretion rate would be beneficial considering the development and promotion of alternatives to animal experiments according to the "3Rs concept." [20] Indeed, most of metal nanomaterials have demonstrated intriguing features for theranostic applications, albeit without possible clinical applications because of persistence issue.…”

Safety assessment of nanoparticles for drug delivery by means of classic in vitro assays and beyond

“…[78] Consequently, oral or topical formulations are better options, which is evident in the orientation of diverse studies.…”

Effects of Cetyltrimethylammonium Bromide on the Toxicity of Gold Nanorods Both In Vitro and In Vivo: Molecular Origin of Cytotoxicity and Inflammation

“…It has been reported that various properties such as size, surface charge, aspect ratio, and coating all contributed to the overall biological effect of Au NRs. Therefore, these parameters were generally taken into accounts when studying the interaction between the Au NRs and the biological systems .…”