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.

Gold nanoparticles have shown potential in photothermal cancer therapy and optoelectronic technology. In both applications, a call for small size nanorods is warranted. In the present work, a one-pot seedless synthetic technique has been developed to prepare relatively small monodisperse gold nanorods with average dimensions (length × width) of 18 × 4.5 nm, 25 × 5 nm, 15 × 4.5 nm, and 10 × 2.5 nm. In this method, the pH was found to play a crucial role in the monodispersity of the nanorods when the NaBH(4) concentration of the growth solution was adjusted to control the reduction rate of the gold ions. At the optimized pH and NaBH(4) concentrations, smaller gold nanorods were produced by adjusting the CTAB concentration in the growth solution. In addition, the concentration of silver ions in the growth solution was found to be pivotal in controlling the aspect ratio of the nanorods. The extinction coefficient values for the small gold nanorods synthesized with three different aspect ratios were estimated using the absorption spectra, size distributions, and the atomic spectroscopic analysis data. The previously accepted relationships between the extinction coefficient or the longitudinal band wavelength values and the nanorods' aspect ratios found for the large nanorods do not extend to the small size domain reported in the present work. The failure of extending these relationships over larger sizes is a result of the interaction of light with the large rods giving an extinction band which results mostly from scattering processes while the extinction of the small nanorods results from absorption processes.

Plasmonic photothermal therapy (PPTT), a type of treatment involving the intravenous or intratumoral injection to introduce gold nanoparticles to cancerous cells and the subsequent exposure to heat-generating near-infrared (NIR) light, is a potentially favorable alternative to traditional treatments of localized tumors such as chemotherapy, radiotherapy, and surgery. The current main concern of PPTT, however, is the feasibility of the treatment in clinical settings. Since PPTT’s initial use 15 years ago, thousands of studies have been published. In this feature article, we summarize the most recent scientific progress, including the efficacy, molecular mechanism, toxicity, and pharmacokinetics of PPTT in vitro with cancer cells and in vivo through mouse/rat model testing, animal clinical cases (such as dogs and cats), and human clinical trials. Given the benefits of PPTT, we believe that it will ultimately become a human clinical treatment that can aid in our ultimate goal of beating cancer.

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.

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