Monday Article #49: Application of Gold Nanoparticles in Cancer Treatment
Cancer is one of the biggest threats to human life. Although the latest technologies are now available for treatment, it still claims millions of lives across the globe each year (Arvizo, Bhattacharya and Mukherjee, 2010). Consequently, there is a need for more advanced and cutting-edge technologies to combat this fatal condition. Cancer therapeutics based on nanoparticles have been presented as a promising method to effectively treat cancer while minimizing side effects. Nanogold (AuNPs) is a type of nanoparticle that is biocompatible and has demonstrated effectiveness in treating cancer because it can penetrate tumours due to its enhanced permeability and retention effect (Arvizo, Bhattacharya and Mukherjee, 2010). The AuNPs' varied therapeutic behaviour is caused by their size and shape. Gold nanoparticles have been used in a variety of applications, including noninvasive in vivo imaging and the evaluation of pathology specimens to detect cancer. AuNPs are simple to make, have a high surface-to-volume ratio, can penetrate biological tissues, economical and have inherent biocompatibility. Additionally, the enhanced permeability and retention (EPR) effect allows the AuNPs to enter tumour cells and makes them less toxic (Arvizo, Bhattacharya and Mukherjee, 2010).
A. Cancer Photothermal Therapy (PTT)
Cancer Photothermal Therapy (PTT) is one of the least invasive cancer treatments with the fewest side effects (Alle et al., 2022). For cancer therapy, it uses near-infrared (NIR) radiation, particularly the NIR-I and NIR-II at 750–1200 nm wavelength to ablate cancer cells and tissues in precise locations with high efficiency. Because of their abnormal vascular structures, tumour cells are ineffective at dissipating heat, which results in hyperthermia that leads to irreversible cellular damages like cell membrane disruption and protein denaturation (Alle et al., 2022). As a result, the risk of cytotoxicity to healthy cells is lower because tumour cells are more sensitive to the PTT effect than healthy tissues (Alle et al., 2022).
PTT is preferred for nanoparticles with a straightforward surface functionalization procedure, plasmon resonance tunability, high photostability and high photothermal conversion efficiency (Alle et al., 2022). Among these nanoparticles, nanogold (AuNPs) with strong localized surface plasmon resonance (LSPR) is recommended for PTT-based cancer treatment. Due to their distinctive optical characteristics, AuNPs have been demonstrated to efficiently absorb light in the NIR region at a wavelength of 700–1350 nm and transform it into the heat-producing PTT effect (Alle et al., 2022).
B. Tumor-targeting nanoparticles
Gold nanoparticles can be decorated with a variety of therapeutic agents to improve the delivery or controlled release of those agents to tumours due to their relatively large surface area and the enhanced permeability and retention (EPR) effect (Lee et al., 2014). To date, biological agents such as tumour necrosis factor, antisense DNA, small interfering RNA (siRNA), paclitaxel and docetaxel have been coated on gold nanoparticles. The lower pH in these endosomes makes it possible for the drug to be released after it has been absorbed by tumour cells and localised there (Lee et al., 2014). In addition, the near-infrared (NIR) laser's ability could also induce hyperthermia, which is capable of helping the drug release at the desired site. For instance, it was discovered that doxorubicin-conjugated hollow gold nanoshells (HAuNSs) stimulated with a NIR laser were more cytotoxic to MDA-MB-231 cells in vitro and further enhanced tumour irradiation in vivo when compared to free or liposomal doxorubicin(Lee et al., 2014). Furthermore, liposomal doxorubicin was more cardiotoxic than stimulated gold conjugates, which is likely because the conjugated form was linked to less free doxorubicin in the blood. Therefore, the stimulated gold conjugates were more effective at ablating tumours (Lee et al., 2014). The polymer polyethylene glycol (PEG) acts as a "stealth" cloak to coat the nanoparticles, preventing their uptake by the reticuloendothelial system (RES) and extending their circulation time and concentration in tumour tissue (Lee et al., 2014). Trastuzumab Conjugates
Theoretically, conjugating gold nanoparticles with trastuzumab has the potential to treat breast cancer cells in two ways: first, by improving the uptake of gold nanoparticles, and second, by overcoming trastuzumab resistance (Lee et al., 2014). When 300 kVp (peak kilovoltage) radiation was applied to HER-2 overexpressing SK-BR-3 breast cancer cells, they experienced 5.1 times as many DNA double-strand breaks in trastuzumab-PEG-AuNPs as compared to PEG-AuNPs. It has also been demonstrated that trastuzumab-AuNR conjugates enter tumor-cell lysosomes and endosomes rather than adhering to the cellular membrane. Trastuzumab-AuNR conjugates have been shown to accumulate in BT474 xenograft tumour tissues in vivo, and adding polyethylene glycol (PEG) to these conjugates can help them maintain their binding affinity during incubation in blood (Lee et al., 2014).
Targeting agents, gene therapy and cytotoxic chemotherapeutic agents
Overexpression of the transferrin receptor has been seen in breast tumours, and it is involved in cellular proliferation (Lee et al., 2014). Therefore, conjugating AuNPs with transferrin would increase the tumoral absorption of AuNPs. Also, luteinizing hormone-releasing hormone receptors (LHRH) are highly expressed in breast cancer cells. When gold-coated iron oxide (Fe3O4) nanoparticles and an analogue of LHRH were conjugated, it was discovered that neither the binding affinity nor the biological activity of the LHRH receptor in LT2 mouse gonadotrope cells was impacted. Additionally, these conjugates significantly affected the survival and growth of the LHRH receptor-expressed MCF-7 and MDA-MB-231 breast cancer cells (Lee et al., 2014). Additionally, small interfering RNA (siRNA) has also been delivered using gold nanoparticles. According to the researchers of one such study, AuNRs conjugated with siRNA against protease-activated receptor-1 (PAR-1) reduced the expression of PAR-1 on the surfaces of MDA-MB-231 cells, which they hypothesized may be helpful in reducing the activity of metastatic cells (Lee et al., 2014).
In conclusion, it is certain that gold nanoparticles indeed have quite a number of applications when it comes to cancer. However, potential therapies must carefully consider their toxicity, which is a significant issue. The toxicity of the nanoparticle core and its capping ligands must be distinguished, even though it has been claimed that gold nanoparticles are naturally non-toxic. Certain ligands may be the cause of some toxicity (Arvizo, Bhattacharya and Mukherjee, 2010). For instance, cationic ligands clearly produce moderate toxicity in vitro. Taking into account how the conjugated ligands may alter pharmacokinetics, biodistribution and potential side effects is also crucial. Similar to this, the packaging technology must be improved if we are to get past tumour penetration and immunogenicity challenges (Arvizo, Bhattacharya and Mukherjee, 2010). Nevertheless, these factors are expected to be resolved with more and more research in the upcoming years and decades. When this happens, we can anticipate that gold nanoparticles can indeed be classified as the gold standard for cancer treatment in the near future.
Alle, M., Sharma, G., Lee, S.-H. and Kim, J.-C. (2022). ‘Next-generation engineered nanogold for multimodal cancer therapy and imaging: clinical perspectives’. Journal of Nanobiotechnology, 20(1). DOI: https://doi.org/10.1186/s12951-022-01402-z. (Accessed: 15 February 2023)
Arvizo, R., Bhattacharya, R. and Mukherjee, P. (2010). ‘Gold nanoparticles: opportunities and challenges in nanomedicine’. Expert Opinion on Drug Delivery, 7(6), pp.753–763. DOI: https://doi.org/10.1517/17425241003777010. (Accessed: 15 February 2023)
Lee, J., Chatterjee, D.K., Lee, M.H. and Krishnan, S. (2014). ‘Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls’. Cancer Letters, 347(1), pp.46–53. DOI: https://doi.org/10.1016/j.canlet.2014.02.006. (Accessed: 15 February 2023)
This article was prepared by Thiiben A/L Krishnan Sami