The Golden Future of Cancer and Nanotechnology

Cancer is one of the leading causes of death worldwide, with the 18.1 million new cases worldwide in 2018 expected to rise to 29.5 million by 2040 [1]. Despite more knowledge about the causes of cancer and improved interventions, cancer mortality rates are still high due to delays in diagnosis and high rates of recurrence. Additionally, current cancer treatments involving chemo or radiation therapy often cause damage to surrounding healthy tissue and result in several side effects. Taking these into account, there is a high demand for the development of effective diagnostics and treatments for cancer.

The field of nanotechnology has seen considerable growth in the past few years, and it is thought that nanotechnology can be utilized to overcome the limitations of conventional cancer treatments. Gold nanoparticles have been of particular interest due to many of their intrinsic properties. Their synwwthesis is relatively simple and their size and shape, which influence stability, mobility and biocompatibility, can be controlled [2]. Precious metals like gold also have a unique optical property called surface plasmon resonance, which allows their electrons to both absorb and scatter light [3]. This property tailors gold nanoparticles for cancer imaging, detection and therapy.

Another important property is the surface functionalization of gold nanoparticles, allowing their surface to be conjugated with a biological compound which could enhance biocompatibility, provide protection, promote specific interactions with cells and allow for targeted drug delivery. Preventing immune recognition and increasing particle circulation time can further maximize the efficiency and minimize harm of such novel treatments. The surface of gold nanoparticles can be coated with polyethylene glycol (PEG) in a process called PEGylation in order to accomplish these aims [4].

One of the various applications of gold nanoparticles is their potential as drug carriers. Traditional drug delivery of chemotherapeutic drugs results in only a fraction of the drug reaching the tumor site [5]. A targeted drug delivery would increase the effectiveness and avoid side effects caused by the drug being delivered to other parts of the body. Gold nanoparticles are able to pass through capillaries to easily reach the cell with lifesaving drugs bound to them. Such targeted delivery to the tumor site could occur either passively or actively. Passive targeting takes advantage of the unique characteristics of solid tumors, such as their leaky vasculature, which enables these nanoparticles to accumulate in the tumor [6]. This is known as the enhanced permeation and retention (EPR) effect. It is important to note that not all tumors exhibit this effect and that there are still limitations. Active targeting, on the other hand, involves the surface of the nanoparticle being conjugated with ligands of tumor specific biomarkers [5]. Methotrexate (MTX), for example, is a common drug used to treat cancer. When bound to gold nanoparticles, MTX displays higher cytotoxicity towards tumor cells and accumulates at a higher level in tumor cells when compared to free MTX, demonstrating that anticancer drugs may be more effective when combined with gold nanoparticles [7]. The ability of gold nanoparticles to target tumor cells also makes them ideal for imaging. A variety of imaging techniques, such as MRI, positron emission tomography (PET) imaging and fluorescence imaging, have been able to detect gold nanoparticles [8]. Medical imaging utilizing gold nanoparticles has the potential to help detect tumors early and make it easier to identify where the tumor ends and where the healthy tissue begins.

Due to their unique optical properties, gold nanoparticles are of particular interest for the application of photothermal therapy (PTT). This kind of treatment involves the gold nanoparticles absorbing light and efficiently converting it into heat, which can then kill the tumor cells. PTT utilizes near infrared light since it is not absorbed by tissues and can treat tumors under the skin [9]. Since the gold nanoparticles would only accumulate in the tumor cells, this method would effectively kill cancer cells while leaving the healthy

cells unharmed. In one study utilizing this approach, tumors were grown in 25 immune-competent mice and PEGcoated gold nanoparticles were intravenously injected. For the treatment group, which consisted of seven mice, the tumors were then exposed to near infrared light using a laser. Within 10 days, all tumors showed complete necrosis and 90 days following treatment, the mice remained healthy and tumor-free [10]. Although this treatment was performed in mice, it is still very promising and the results demonstrate that PTT utilizing gold nanoparticles is effective. Additionally, such a treatment is minimally invasive, easy to perform, and can treat tumors in regions where surgery is not feasible.

As of now, this technology is still in its infancy and there are not many clinical trials being conducted. That being said, one early stage clinical trial has demonstrated remarkable results. The study used gold-silica nanoparticles and PTT for the treatment of prostate cancer. Sixteen men diagnosed with low or intermediate risk localized prostate

cancer underwent treatment [11]. The nanoparticles were infused and the tumors were exposed to a near infrared laser. Biopsies revealed that PTT was successfully achieved in fifteen of the sixteen men and no serious adverse

events were reported [11]. Ultimately, the trial demonstrated that photothermal therapy utilizing nanoparticles is both a safe and feasible method to destroy prostate tumors.

While gold nanoparticles do show promise and potential to diagnose and treat cancer in the future, it is also important to consider their current limitations. One cause of concern is that gold nanoparticles might have unintended side effects on human health. Certain properties may cause these gold nanoparticles to be toxic, which can be influenced by factors such as size, shape, surface charge and composition [5]. One of the main challenges is that it is hard to determine the response of the biological system to nanoparticles in different cells or tissues due to their complexity and heterogeneity. Additionally, the fate of nanoparticles and how they will be excreted from the body is also an important aspect that needs to be considered [5]. Lastly, more information on whether gold nanoparticles impact epigenetics and gene expression patterns is needed. Taking these factors into consideration, gold nanoparticles offer a unique opportunity to improve cancer diagnostics and treatments; however, more research is needed before they can be translated into clinically accepted cancer diagnostics and treatments. •