Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines.

Cancer is a global epidemic disease responsible for over ten millions death worldwide. The early diagnosis and the precise treatment with reduced adverse reactions are the main goal worldwide. In this study, we produced, characterized and evaluated (in vitro) in three different cancer cell lines (protaste, breast and melanoma) a radioactive gold nanocluster (R-AuNC) (198Au25(Capt)18). The pharmacokinetics as the influence in the ABC transporter (MRP1 Efflux Transporter Protein) was also evaluated. The results showed that R-AuNC (198Au25(Capt)18) are capable to kill the cancer cells lines of protaste, breast and melanoma. The pharmacokinetics showed a fast clearance and great volume of distribution, confirming the use of R-AuNC as nanomedicine for cancer treatment. Finally, the ABC transporter assay corroborated that the R-AuNC (198Au25(Capt)18) has no risk of being pumped out of cells by this efflux transporter. The results validate the use of gold nanoparticles as therapeutic nanomedicine for cancer treatment.

Synthesis and Biodistribution Study of Biocompatible 198Au Nanoparticles by use of Arabinoxylan as Reducing and Stabilizing Agent.

Radioactive gold-198 is a useful diagnostic and therapeutic agent. Gold in the form of nanoparticles possesses even more exciting properties. This work aimed at arabinoxylan-mediated synthesis and biodistribution study of radioactive gold nanoparticles (198AuNPs). The particles were synthesized by mixing suspension of arabinoxylan with H198AuCl4 without use of any additional reducing and stabilizing agents. An aqueous suspension of arabinoxylan was added to a H198AuCl4 solution, which resulted in reduction of Au3+ to 198AuNPs. Biodistribution was studied in vitro and in rabbit. The particles having exceptional stability were readily formed. Highest radioactivity was recorded in spleen after 3 h followed by liver, heart, kidney, and lungs after i.v. administration. After 24 h, the activity was not detectable in the spleen; it accumulated in the liver. However, after oral administration, the activity mainly accumulated in the colon. In serum proteins, the distribution was α1-globulin 6.5%, α2-globulin ~ 2%, ß-globulin ~ 1%, γ-globulin 0.7%, and albumin 0.7% of the administered dose. This indicates a low protein binding implying high bioavailability of the particles. The cytotoxicity study showed that the particles were inactive against HeLa cell line and Agrobacteriumtumefaciens. Highly stable 198AuNPs reported in this work have the potential for targeting the colon. They show affinity for globulins, the property that can be used in the study of the immune system.

Internalization capabilities of gold-198 nanoparticles: Comparative evaluation of effects of chitosan agent on cellular uptake into MCF-7.

In this study, internalization of positively charged chitosan-coated nanoparticles (198AuNPs@chitosan) on MCF-7 cells was investigated by γ-ray spectroscopy and then statistically compared to that of 198Au and negatively charged citrate-stabilized nanoparticles (198AuNPs). Sub-50 nm 198AuNPs@chitosan had a higher internalization compared to 198Au and 198AuNPs (p < 0.05). More cellular uptake of 198AuNP@chitosan means a higher dose of radioactivity to the tumor cells which, in turn, more effective treatment of the cancer.

Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer.

Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the (198)Au ß-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible (198)AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of (198)AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable (198)AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.

Absorbed dose profiles for radionuclides of frequent use in radiation synovectomy.

Absorbed dose profiles are presented for radionuclides of frequent or potential use in radiation synovectomy, an intraarticular technique aimed at treating rheumatoid arthritis through direct and highly selective irradiation of inflamed synovium. The radionuclides investigated were 198Au, 165Dy, 32P, 186Re, 90Y, and 166Ho. These profiles reveal the absorbed dose imparted per unit activity of injected radionuclide (Gy/mCi) as a function of penetration distance (mm) to major components of the arthritic synovial joint. Their usefulness is twofold: they can be employed to select the radionuclide best suited to achieving the proper depth of penetration in tissue (approximating the thickness of the inflamed synovium) and to determine, a priori, the necessary dose of radioactivity (delivering an absorbed dose sufficient to effectively treat all the diseased tissue). The extent of radiation of other synovial joint components, such as bone and articular cartilage, and how the advancing rheumatoid arthritis can be expected to alter the extent and pattern of absorbed dose penetration in the joint are also discussed.

Effect of exercise on redistribution and clearance of inhaled particles from hamster lungs.

Does exercise alter the redistribution and clearance of particles from the lungs? Sedentary hamsters and hamsters that were exercise trained by voluntary wheel running for the previous 5 wk were exposed to a 198Au-labeled aerosol for 25 min. Six trained and 6 sedentary animals were killed within 5 min after the exposure (day 0); the same number were killed 5 days later. The trained hamsters ran ad libitum during those 5 days. The lungs of all animals were excised, dried at total lung capacity, sliced into 1-mm-thick sections, and dissected into pieces that were counted for radioactivity and weighed. On day 0, trained hamsters had 80% more particles per milligram of lung than sedentary hamsters, although both were exposed under identical conditions of restraint. After five days, exercising hamsters cleared 38% of the particles present at day 0, whereas sedentary animals removed only 15%. Significant clearance was observed from the middle lung regions of sedentary hamsters and from all lung regions in exercising hamsters. We conclude that exercise can enhance the redistribution and clearance of particles from the lungs; the mechanisms responsible are as yet unclear.

The clearance of colloidal particles by Kupffer cells in collagen disease.

The Kupffer cells clearance of colloidal 198Au particles with a diameter of 200-300 A was estimated in 14 subjects with different collagen diseases: 7 without previous treatment and 7 under immunodepressive treatment compared to 10 controls. No difference between the subjects with collagen disease and controls was observed. The group with collagen disease under immunodepressive treatment has lower Kupffer cells clearance for colloidal gold particles than non-treated patients, without statistical significance.