Gold Nanoparticles in Cancer Therapy

From the oldest metal element to a versatile nanomaterial, gold a powerful element to serve human life, culture and health. Gold will be always have the irreplaceable role forever. The surface chemistry of functionalized gold nanoparticles (Au NPs) plays a crucial role in the effective utilization in health-related applications like cancer therapy. It mainly depends on the physical and chemical reactions between the molecules and gold nanoparticles. To meet the basic needs of various applications, the surface properties of gold nanoparticles can be tailored and precisely controlled [1]. Generally, these gold nanoparticles have unique physical and chemical properties, which can be widely used for a broad range of applications from prophylaxis to diagnosis and also for other treatments. Meanwhile, gold has an excellent conductivity, malleable and ductile which can make it stretchable or compressible to arbitrary shape, quite biocompatible, as some edible gold foils are added to cakes, tea, and cosmetics because of its good properties to human’s health. When the size of gold is in the nanometer scale from (1–100 nm), then it exhibits completely different properties to that of the bulk gold, especially its change in the optical properties. Hence, these unique properties of gold have been applied in various fields such as therapeutic agents, sensing probes, drug delivery systems in biological and pharmaceutical applications [2,3].

Cancer is considered to be one of the deadly diseases in humans. Cancer treatment or therapy is still a scientific challenge due to the lack of adequate miracle drugs, diversity of the chronic disease and the variation in personal expression. Currently, the most effective mode of cancer treatment which is widely used is the surgery in combination with radiotherapy and chemotherapy. However, the increasing drug resistance makes it urgent to develop new therapeutic strategies and highly specific medicines of easily invasive and metastatic properties of cancer cells. Therefore, nanomedicine offers some unique features and emerged as a promising strategy to enhance traditional therapeutic efficacy. Among various nanomaterials that have been investigated for cancer therapeutic applications, Au NPs are found to be broadly studied benefiting from their unique electrical, chemical, and optical properties with excellent biocompatible features, as well as the ease of synthetic manipulation and precise control over their physicochemical properties [4,5].

Figure 1. Gold Nanoparticles in Treatment of Prostate Cancer. Image credited to Aakash Jha et al., YouTube.

Au NPs shows the radiation dose enhancement effect in vivo, and have aroused great interest in the field of Au NP-based radiosensitization for oncology. Tailoring the beam of X-ray irradiation and treatment with Au NPs can significantly enhance the survival of mice. In addition to the physical enhancement effect, the researchers have also discovered some new approaches in radiosensitization of chemical enhancement (DNA damage and radical production) and biological enhancement (ROS-induced oxidative stress, inhibition of DNA repair and cell cycle disruption) [6].

Metabolizable ultra small Au NPs (core size of approx. 1.5 nm) with a biocompatible coating ligand (glutathione, GSH) will strongly enhance the cancer radiotherapy. However, the GSH–Au NPs scan can preferentially accumulate in tumors with an improved enhanced permeability and retention effect. After the treatment, GSH–Au NPs can be efficiently cleared through the kidneys which minimize further potential side effects [7].

Zhang et al., have developed SiO₂-coated rod-like Au NPs (Au@SiO₂) as a novel cancer theranostic agent. The large surface area with a high cavity of SiO₂can significantly improve the loading of chemotherapy drugs such as doxorubicin (DOX) hydrochloride. NIR laser irradiation can enhance the DOX release from Au@SiO₂, as well as generate a high temperature provided with the combined therapeutic modes of chemotherapy and photothermal therapy [8].

Figure 2. Cancer therapy using Au NPs. [6].

An alternative to delivering drugs and photosensitizers for cancer therapy, Au NP-assisted delivery of siRNA can be a highly effective treatment of cancers deep in the body. siRNA, a short double-stranded RNA sequence, can specifically degrade the complementary mRNA and will inhibit the production of target proteins. However, the efficiency of the siRNA is very low, because it can be rapidly degraded by nucleases in the blood stream. Hence, to increase the efficiency, surface dendronized Au NPs have a positively charged surface for electrostatic complexation with negatively charged siRNA. Hence, the Au NPs/siRNA complex shows enhanced in vitro transfection into cells compared to the siRNA. Huschka et al., have also used polylysine-modified Au nanoshells for delivery and light-controlled release of siRNA. When it is exposed to the laser irradiation, the release efficiency is higher than the single thermal-induced release with uncontrolled passive release. For in vitro cell models, the laser treatment will increase the down regulation of targeted proteins [9].

In conclusion, the carbohydrates and polymer conjugation, optimal surface chemistry endowed by small molecules, can greatly help the immunogenic presentation of antigens for developing vaccines and are highly efficient for the delivery of therapeutic drugs for cancer treatments. However, there are still a lot of things for researchers to design and synthesize versatile ligands/polymers to regulate the surface chemistry of Au NPs with very high efficiency and as well as enhanced biocompatibility with minimized side effects.

Our SNB Team recommended this new research to help the reader to know about Au NPs with various ligands/polymers, complexes and by optimizing slightly its surface properties, can be applied to our biological system for curing the medical problems mainly for the cancer therapy or treatment and also for other health-related treatments.

References

J. Zhang et al.,Chem. Sci. 11, 923 (2020).
J. Sun, et al., Chem. Soc. Rev. 43,6239 (2014).
P. Kesharwani, et al., Prog. Mater. Sci. 103, 484 (2019).
Y. Wang, et al., Adv. Mater., 30,1705660 (2018).
S. Mitragotri, et al., ACS Nano. 9, 6644 (2015).
S. Her, et al., Adv. Drug Delivery Rev.109, 84 (2017).
X.-D. Zhang, et al., Adv. Healthcare Mater. 3, 133 (2014).
Z. Zhang, et al., Adv. Mater. 24, 1418 (2012).
R. Huschka, et al., ACS Nano. 6, 7681 (2012).

Blog Written By

Dr. Y. Sasikumar

School of Materials Science and Engineering,

Tianjin University of Technology, China

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Dr. A. S. Ganeshraja

Dr. S. Chandrasekar

Dr. K. Rajkumar

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