Optimization of the GSH-Mediated Formation of Mesoporous Silica-Coated Gold Nanoclusters for NIR Light-Triggered Photothermal Applications

Abstract

Cancer light-triggered hyperthermia mediated by nanomaterials aims to eliminate cancer cells by inducing localized temperature increases to values superior to 42 °C, upon irradiation with a laser. Among the different nanomaterials with photothermal capacity, the gold-based nanoparticles have been widely studied due to their structural plasticity and advantageous physicochemical properties. Herein, a novel and straightforward methodology was developed to produce gold nanoclusters coated with mesoporous silica (AuMSS), using glutathione (GSH) to mediate the formation of the gold clusters. The obtained results revealed that GSH is capable of triggering and control the aggregation of gold nanospheres, which enhanced the absorption of radiation in the NIR region of the spectra. Moreover, the produced AuMSS nanoclusters mediated a maximum temperature increase of 20 °C and were able to encapsulate a drug model (acridine orange). In addition, these AuMSS nanoclusters were also biocompatible with both healthy (fibroblasts) and carcinogenic (cervical cancer) cells, at a maximum tested concentration of 200 μg/mL. Nevertheless, the AuMSS nanoclusters’ NIR light-triggered heat generation successfully reduced the viability of cervical cancer cells by about 80%. This confirms the potential of the AuMSS nanoclusters to be applied in cancer therapy, namely as theragnostic agents.

In situ formation of alginic acid‐gold nanohybrids for application in cancer photothermal therapy

“…[25,27] Moreover, it is worth noticing that in conjugation with a simpler methodology, the duration was also maintained in the 2 h period, contrasting with the longer conventional gold nanoparticles' synthesis, usually from hours up to days. [15,26] The successful synthesis of Au-Alg-NH was initially confirmed by TEM (Figures 2A and S1). The analysis of TEM images demonstrates that the Au-Alg-NH acquires an anisotropic spike-like shape, resembling the gold nanostars, with gold nucleation occurring throughout the Alg matrix in the nanohybrids.…”

“…[ 25,27 ] Moreover, it is worth noticing that in conjugation with a simpler methodology, the duration was also maintained in the 2 h period, contrasting with the longer conventional gold nanoparticles’ synthesis, usually from hours up to days. [ 15,26 ]…”

“…[10] Moreover, this localized temperature increase can sensitize the tumor cells to other therapeutics, trigger the host immunity, enhance the blood flow in the tumor region, and even promote cell apoptosis and necrosis when reaching temperatures higher than 45 • C. [10][11][12][13][14] However, the application of gold nanoparticles is hindered by the high reactivity with thiol groups, which increases the interactions between nanoparticles and proteins, promoting aggregation, size increase, and recognition by the immune system. [15] Moreover, the gold nanoparticles can also undergo thermal degradation when exposed to high-intensity radiations. [16] To address these issues, gold nanoparticles are often combined with other materials, inorganic (e.g., silica) and/or organic (e.g., polymers), to improve nanoparticles' biocompatibility, stability, and tumor specificity.…”

“…However, the application of gold nanoparticles is hindered by the high reactivity with thiol groups, which increases the interactions between nanoparticles and proteins, promoting aggregation, size increase, and recognition by the immune system. [ 15 ] Moreover, the gold nanoparticles can also undergo thermal degradation when exposed to high‐intensity radiations. [ 16 ] To address these issues, gold nanoparticles are often combined with other materials, inorganic (e.g., silica) and/or organic (e.g., polymers), to improve nanoparticles’ biocompatibility, stability, and tumor specificity.…”

Nanomaterials in Drug Delivery Applications

“…The EC coating resulted in a sustained release of Tamoxifen, increasing the time to release 50% of the drug from 1.89 h to 12.79 h. Therefore, the utilization of nanomaterials provides new approaches for researchers to tailor pharmacokinetics and pharmacodynamics, which can also be an essential step for drug repurposing and the development of more effective therapeutics. Moreover, nanomaterials can also be engineered to combine the drug delivery capacity with other therapeutic approaches, such as photothermal therapy, as demonstrated by Fernandes and colleagues with the development of mesoporous silica-coated gold nanoclusters [ 4 ].…”