Biodistribution, Clearance, and Toxicology of Polymeric Micelles Loaded with 0.9 or 5 nm Gold Nanoparticles.
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.
Ajlan
A
Al Zaki
James Z
JZ
Hui
Elizabeth
E
Higbee
Andrew
A
Tsourkas
D000818:Animals; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D007700:Kinetics; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D009928:Organ Specificity; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D014018:Tissue Distribution; D014781:Viscera / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*
D008823:Micelles; D053769:Nanocapsules; D011108:Polymers; D006046:Gold