Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold–Silica Nanoshells)

Abstract

Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

“…10 Phase II clinical trials have been announced (http:// www.cytimmune.com/user/register#pipeline). 11 Several other gold-chemotherapy agents, such as Auroshell 12,13 and Aurimune, are under clinical trials or seeking approval. 9,10,[12][13][14] Noteworthy, at the beginning of 2013, the international pharmaceutical company AstraZeneca in partnership with CytImmune focused on developing a cancer nanomedicine based on AuNPs.…”

“…11 Several other gold-chemotherapy agents, such as Auroshell 12,13 and Aurimune, are under clinical trials or seeking approval. 9,10,[12][13][14] Noteworthy, at the beginning of 2013, the international pharmaceutical company AstraZeneca in partnership with CytImmune focused on developing a cancer nanomedicine based on AuNPs. 15 The successful application of AuNPs as tools for cancer treatment is mainly associated to their unique physicochemical properties and acceptable biocompatibility.…”

In vivo photothermal treatment by the peritumoral injection of macrophages loaded with gold nanoshells

“…Presumably, the NSs aggregated into coarse particles cannot be passively distributed to other organs. This result means that the local injection of NSs might overcome the cytotoxicity problem which is caused by the uncontrollable circulation of nanoparticles, such as after intravenous injection [18][19][20]. …”

Gold Nanoparticle Surface Functionalization: A Necessary Requirement in the Development of Novel Nanotherapeutics

“…A second GNP clinical trial plans to use AuroShell® particles (Nano-spectra Biosciences Inc, Houston, TX) administered intravenously, followed by exposure to an 808 nm laser as photothermal ablation therapy for the treatment of head and neck cancer [7]. In vivo data from the same study demonstrated that the 155 nm nanoshells capped with 5000 M w PEG have the ability to accumulate at the tumour site in canines with brain tumours; human trials are ongoing as of September 2014.…”