A one-step homogeneous immunoassay for the detection of a prostate cancer biomarker, free-PSA (prostate specific antigen), was developed using gold nanoparticle probes coupled with dynamic light scattering (DLS) measurements. A spherical gold nanoparticle with a core diameter around 37 nm and a gold nanorod with a dimension of 40 by 10 nm were first conjugated with two different primary anti-PSA antibodies and then used as optical probes for the immunoassay. In the presence of antigen f-PSA in solution, the nanoparticles and nanorods aggregate together into pairs and oligomers through the formation of a sandwich type antibody-antigen-antibody linkage. The relative ratio of nanoparticle-nanorod pairs and oligomers versus individual nanoparticles was quantitatively monitored by DLS measurement. A correlation can be established between this relative ratio and the amount of antigen in solution. The light scattering intensity of nanoparticles and nanoparticle oligomers is several orders of magnitude higher than proteins and other typical molecules, making it possible to detect nanoparticle probes in the low picomolar concentration range. f-PSA in the concentration range from 0.1 to 10 ng/mL was detected by this one-step and washing-free homogeneous immunoassay.
Cancer is the current leading cause of death worldwide, responsible for approximately one quarter of all deaths in the USA and UK. Nanotechnologies provide tremendous opportunities for multimodal, site-specific drug delivery to these disease sites and Au nanoparticles further offer a particularly unique set of physical, chemical and photonic properties with which to do so. This review will highlight some recent advances, by our laboratory and others, in the use of Au nanoparticles for systemic drug delivery to these malignancies and will also provide insights into their rational design, synthesis, physiological properties and clinical/preclinical applications, as well as strategies and challenges toward the clinical implementation of these constructs moving forward.
The development of new and improved photothermal contrast agents for the successful treatment of cancer (or other diseases) via plasmonic photothermal therapy (PPTT) is a crucial part of the application of nanotechnology in medicine. Gold nanorods (AuNRs) have been found to be the most effective photothermal contrast agents, both in vitro and in vivo. Therefore, determining the optimum AuNR size needed for applications in PPTT is of great interest. In the present work, we utilized theoretical calculations as well as experimental techniques in vitro to determine this optimum AuNR size by comparing plasmonic properties and the efficacy as photothermal contrast agents of three different sizes of AuNRs. Our theoretical calculations showed that the contribution of absorbance to the total extinction, the electric field, and the distance at which this field extends away from the nanoparticle surface all govern the effectiveness of the amount of heat these particles generate upon NIR laser irradiation. Comparing between three different AuNRs (38 × 11, 28 × 8, and 17 × 5 nm), we determined that the 28 × 8 nm AuNR is the most effective in plasmonic photothermal heat generation. These results encouraged us to carry out in vitro experiments to compare the PPTT efficacy of the different sized AuNRs. The 28 × 8 nm AuNR was found to be the most effective photothermal contrast agent for PPTT of human oral squamous cell carcinoma. This size AuNR has the best compromise between the total amount of light absorbed and the fraction of which is converted to heat. In addition, the distance at which the electric field extends from the particle surface is most ideal for this size AuNR, as it is sufficient to allow for coupling between the fields of adjacent particles in solution (i.e., particle aggregates), resulting in effective heating in solution.
Dynamic light scattering (DLS) is an analytical tool used routinely for measuring the hydrodynamic size of nanoparticles and colloids in a liquid environment. Gold nanoparticles (GNPs) are extraordinary light scatterers at or near their surface plasmon resonance wavelength. In this study, we demonstrate that DLS can be used as a very convenient and powerful tool for gold nanoparticle bioconjugation and biomolecular binding studies. The conjugation process between protein A and gold nanoparticles under different experimental conditions and the quality as well as the stability of the prepared conjugates were monitored and characterized systematically by DLS. Furthermore, the specific interactions between protein A-conjugated gold nanoparticles and a target protein, human IgG, can be detected and monitored in situ by measuring the average particle size change of the assay solution. For the first time, we demonstrate that DLS is able to directly and quantitatively measure the binding stoichiometry between a protein-conjugated GNP probe and a target analyte protein in solution.
Nanotechnology is a rapidly growing area of research in part due to its integration into many biomedical applications. Within nanotechnology, gold and silver nanostructures are some of the most heavily utilized nanomaterial due to their unique optical, photothermal, and facile surface chemical properties. In this review, common colloid synthesis methods and biofunctionalization strategies of gold and silver nanostructures are highlighted. Their unique properties are also discussed in terms of their use in biodiagnostic, imaging, therapeutic, and drug delivery applications. Furthermore, relevant clinical applications utilizing gold and silver nanostructures are also presented. We also provide a table with reviews covering related topics.
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