Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity.

Development of cancer receptor-specific gold nanoparticles will allow efficient targeting/optimum retention of engineered gold nanoparticles within tumors and thus provide synergistic advantages in oncology as it relates to molecular imaging and therapy. Bombesin (BBN) peptides have demonstrated high affinity toward gastrin-releasing peptide (GRP) receptors in vivo that are overexpressed in prostate, breast, and small-cell lung carcinoma. We have synthesized a library of GRP receptor-avid nanoplatforms by conjugating gold nanoparticles (AuNPs) with BBN peptides. Cellular interactions and binding affinities (IC(50)) of AuNP-BBN conjugates toward GRP receptors on human prostate cancer cells have been investigated in detail. In vivo studies using AuNP-BBN and its radiolabeled surrogate (198)AuNP-BBN, exhibiting high binding affinity (IC(50) in microgram ranges), provide unequivocal evidence that AuNP-BBN constructs are GRP-receptor-specific showing accumulation with high selectivity in GRP-receptor-rich pancreatic acne in normal mice and also in tumors in prostate-tumor-bearing, severe combined immunodeficient mice. The i.p. mode of delivery has been found to be efficient as AuNP-BBN conjugates showed reduced RES organ uptake with concomitant increase in uptake at tumor targets. The selective uptake of this new generation of GRP-receptor-specific AuNP-BBN peptide analogs has demonstrated realistic clinical potential in molecular imaging via x-ray computed tomography techniques as the contrast numbers in prostate tumor sites are severalfold higher as compared to the pretreatment group (Hounsfield unit = 150).

Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies.

Gold nanoparticles (AuNPs) have exceptional stability against oxidation and therefore will play a significant role in the advancement of clinically useful diagnostic and therapeutic nanomedicines. Despite the huge potential for a new generation of AuNP-based nanomedicinal products, nontoxic AuNP constructs and formulations that can be readily administered site-specifically through the intravenous mode, for diagnostic imaging by computed tomography (CT) or for therapy via various modalities, are still rare. Herein, we report results encompassing: 1) the synthesis and stabilization of AuNPs within the nontoxic phytochemical gum-arabic matrix (GA-AuNPs); 2) detailed in vitro analysis and in vivo pharmacokinetics studies of GA-AuNPs in pigs to gain insight into the organ-specific localization of this new generation of AuNP vector, and 3) X-ray CT contrast measurements of GA-AuNP vectors for potential utility in molecular imaging. Our results demonstrate that naturally occurring GA can be used as a nontoxic phytochemical construct in the production of readily administrable biocompatible AuNPs for diagnostic and therapeutic applications in nanomedicine.

Gold nanoparticle contrast in a phantom and juvenile swine: models for molecular imaging of human organs using x-ray computed tomography.

RATIONALE AND OBJECTIVES: The purpose of this study was to demonstrate the application of gold nanoparticles (AuNP) as a contrast agent for a clinical x-ray computed tomography (CT) system using a phantom and juvenile swine. MATERIALS AND METHODS: A tissue-mimicking phantom with spherical inclusions containing known concentrations of Au was scanned. Swine were injected with gum Arabic stabilized Au nanoparticles (GA-AuNP), up to 85 mg kg(-1) body weight. CT scans were performed before and after the injections. Changes in Hounsfield unit (HU) values between pre- and post- injection scans were evaluated and compared to postmortem determinations of Au uptake. Average uptake of GA-AuNP in the liver of the swine was 380 microg per gram of liver and 680 microg per gram of spleen. RESULTS: Concentrations of Au in tissues increased the CT numbers in liver by approximately 22 HU per mg Au concentration at 80 kVp and 27 HU per mg Au concentration at 140 kVp. These data were consistent with HU changes observed for similar concentrations in the phantom. CONCLUSIONS: AuNP-based contrast agents may be useful in x-ray based CT. This study provides data for determining concentrations of AuNP in comparison to other contrast materials.

Facile and General Method for Synthesis of Sugar Coated Gold Nanoparticles.

This letter describes a general method for the preparation of carbohydrate coated gold nanoparticles. The generality of this method has been demonstrated by surface coating AuNPs with the following sugars: glucose (monosaccharide); sucrose, maltose, or lactose (disaccharides); raffinose (trisaccharide); and starch (polysaccharide). The non-toxic, water-soluble phosphino aminoacid P(CH(2)NHCH(CH(3)-)COOH)(3), THPAL, has been used as a reducing agent in this process. The sizes of sugar coated AuNPs that have been generated in this study are: 30 ± 8 nm (Glucose), 10 ± 6 nm (sucrose), 8 ± 2 nm (maltose), 3 ± 1 nm (lactose), 6 ± 2 nm (raffinose), and 39 ± 9 nm (starch).

Nanocompatible chemistry toward fabrication of target-specific gold nanoparticles.

Nanocompatible chemistry which utilizes a novel nontoxic phosphino amino acid as a reducing agent has resulted in the development of therapeutically useful gold nanoparticles under biologically benign media. Stabilization of gold nanoparticles by the edible gum arabic matrix has provided an effective pathway toward in vivo stable target-specific gold nanoparticles.