ABSTRACT
Gold nanoparticles (GNPs) are advantageous as an adjuvant in the design of effective vaccines and in the preparation of high-affinity antibodies to haptens and complete antigens. Another method of activating immunocompetent cells with colloidal gold is to conjugate GNPs with CpG oligodeoxynucleotides (ODNs). We examined how the size and shape of GNPs and various combinations of GNPs and CpG ODNs 1826 affect the immune response. When animals were injected with a model antigen (BSA) coupled to gold nanospheres (diameters, 15 and 50nm), nanorods, nanoshells, and nanostars, the titers of the resultant antibodies differed substantially. The antibody titers decreased in the sequence GNPs-50nm>GNPs-15nm>nanoshells>nanostars>nanorods>native BSA. We conclude that 50 and 15nm gold nanospheres are the optimal antigen carrier and adjuvant for immunization. The highest titer of anti-BSA antibodies was detected in the blood serum of mice immunized simultaneously with BSA-GNP and CpG-GNP conjugates.
Subject(s)
Gold Colloid/therapeutic use , Nanoparticles/therapeutic use , Vaccines/immunology , Adjuvants, Immunologic , Animals , Animals, Outbred Strains , Antibody Formation , Gold/chemistry , Mice , Oligodeoxyribonucleotides/chemistry , Particle Size , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/immunology , Vaccines/chemistrySubject(s)
Gold Colloid/adverse effects , Spleen/diagnostic imaging , Splenic Diseases/chemically induced , Arthritis, Rheumatoid/drug therapy , Diagnosis, Differential , Female , Gold Colloid/therapeutic use , Humans , Middle Aged , Radiography , Spleen/drug effects , Splenic Diseases/diagnostic imagingABSTRACT
Since their initial description in 1857, gold nanoparticles have been used extensively in the fields of diagnostics and therapeutics. Now, gold nanoparticles are engineered to target the delivery of potent anti-cancer therapeutics to solid tumors to improve either their safety or efficacy or both. Described in this chapter is the development of one such nanotherapeutic, termed CYT-6091, that targets the delivery of tumor necrosis factor alpha (TNF) to solid tumors. Outlined in the presentation is a discussion of nanoparticles and specifically colloidal gold, an historical review on the biology of TNF and its limited use in the clinic when administered systemically, and finally, how gold nanoparticles bound with TNF may improve the safety and efficacy profiles of TNF.
Subject(s)
Drug Delivery Systems/methods , Gold Colloid/therapeutic use , Nanomedicine/methods , Nanoparticles/therapeutic use , Neoplasms/therapy , Drug Screening Assays, Antitumor , Humans , Tumor Necrosis Factor-alpha/therapeutic useABSTRACT
Thermal therapies such as hyperthermia, radiofrequency ablation, cryoablation, etc. have shown great potential and are gaining increasing clinical acceptance in the treatment of solid tumors. However, these treatment modalities are limited by the size of tumor that can be treated, incomplete tumor kill, and damage to adjacent normal tissues. To address these limitations, the concept of adjuvant-assisted thermal therapies has been proposed and tested to enhance the tumor destructive effects of thermal therapies. CYT-6091, a pegylated colloidal gold nanoparticle containing TNF-alpha bound to its surface, has been extensively investigated in our lab as an adjuvant to enhance thermal therapies. This paper describes our investigations of nanoparticle enhanced thermal therapies in various preclinical and translational models of solid tumors.
Subject(s)
Gold Colloid/therapeutic use , Hyperthermia, Induced , Nanoparticles/therapeutic use , Animals , Female , Fibrosarcoma/therapy , Mammary Neoplasms, Experimental/therapy , Mice , Mice, Inbred A , Neoplasms/therapy , Sarcoma, Experimental/therapy , Tumor Necrosis Factor-alpha/therapeutic useABSTRACT
Gold colloidal nanoparticles were prepared by the liquid laser ablation of a gold metal plate in water and also by the citrate reduction of HAuCl(4).4H2O. The gold colloidal nanoparticles with the plasmonic band strongly absorb light, which is converted to the photothermal energy. This photothermal energy gives a cytotoxic effect on epithelial carcinoma cells. Interestingly, we found that the size and shape of the nanoparticles are changed by light during the photothermal process in vitro. The cervical carcinoma cell line (HeLa cell) was incubated with the colloidal gold nanoparticles and then exposed to continuous visible light at 400-600 nm with UV- and heat-cutoff filters. The distinct cell-killing effect was observed by this procedure. In the absence of the gold colloidal nanoparticles, only a small amount of cells were photothermally destroyed.
Subject(s)
Carcinoma/radiotherapy , Cell Survival/radiation effects , Gold Colloid/therapeutic use , Metal Nanoparticles/therapeutic use , Surface Plasmon Resonance , Uterine Cervical Neoplasms/radiotherapy , Female , Gold Colloid/chemistry , HeLa Cells , Humans , Metal Nanoparticles/chemistry , Particle Size , PhotochemistryABSTRACT
Metallic gold (Au degrees ) is a likely biotransformation product of monovalent gold, Au(I) whenever it is dissociated from in vivo ligands, Au degrees being formed either by bioreduction or by spontaneous dismutation (with co-production of trivalent gold). This review discusses the preparation and some biologically relevant properties of colloidal metallic gold (CMG) in its nano-particulate form. Tyndall's purple, a well characterised preparation of CMG, shows potent anti-arthritic activity in rats, approximately 10(3) times that of sodium aurothiomalate (Myocrysin). Even more remarkable is its broader spectrum of action in rats compared to this classic DMARD.
