The emergence of nanotechnology has provided scientists with the tools to engineer materials at the atomic and molecular scale. Gold nanoparticles (GNPs) have become a focal point of cancer research within this field of nanomedicine. The unique physical and chemical properties of these minute gold structures allow them to interface with biological systems in ways that conventional drugs cannot. By functioning in drug delivery, thermal ablation, and radiation enhancement, gold nanoparticles offer a promising pathway toward more precise and less toxic cancer treatments.
Defining Gold Nanoparticles for Medicine
Gold nanoparticles are ultrafine particles of gold, typically ranging from 1 to 100 nanometers in diameter. At this small scale, gold exhibits properties distinct from its bulk form, making it valuable for biomedical applications. Gold’s inherent inertness translates to high biocompatibility and low toxicity when introduced into the body.
The surface of a gold nanoparticle can be easily modified, a process known as functionalization, by attaching various molecules like polymers, antibodies, or drug compounds. This allows researchers to tailor the particle’s behavior for specific purposes, such as enhancing stability in the bloodstream or facilitating targeted binding to cancer cells. The most unique feature is the Localized Surface Plasmon Resonance (LSPR), a phenomenon where the free electrons on the gold surface oscillate collectively when struck by light. This LSPR effect results in the particles absorbing and scattering light with extreme efficiency, an optical property that can be precisely tuned by controlling the particle’s size and shape.
Gold Nanoparticles as Targeted Drug Carriers
Gold nanoparticles serve as carriers for delivering chemotherapy drugs directly to malignant tumors. Chemotherapeutic agents can be chemically attached to the GNP surface, protecting the drug from premature degradation while in circulation. This design takes advantage of two primary targeting strategies to concentrate the drug payload at the disease site.
The first strategy is passive targeting, which utilizes the Enhanced Permeability and Retention (EPR) effect common in solid tumors. Cancerous tissue grows rapidly, leading to the formation of structurally flawed blood vessels that are unusually leaky, with pores up to 1 micrometer in size. Nanoparticles can easily squeeze through these large gaps and accumulate in the tumor microenvironment, where they are then retained due to poor lymphatic drainage.
The second, more refined method is active targeting, which involves functionalizing the GNP surface with specific ligands, such as antibodies, peptides, or vitamins. These ligands are designed to recognize and bind with high affinity to receptors that are overexpressed on the surface of cancer cells. By engaging these receptors, the GNPs are actively taken up by the cancer cells via endocytosis, significantly increasing the local drug concentration and improving therapeutic selectivity.
Destroying Tumors with Heat and Light
One application of gold nanoparticles is Plasmonic Photothermal Therapy (PTT), which uses light to generate localized heat and destroy cancer cells. This mechanism relies on the LSPR property, where the GNPs absorb light energy and instantly convert it into thermal energy. To reach deep-seated tumors, the GNPs must be tuned to absorb light within the Near-Infrared (NIR) spectrum, specifically the first NIR window between 650 and 850 nanometers.
NIR light is used because it passes through biological tissue, such as skin and muscle, with minimal absorption, allowing the external laser to reach the tumor without damaging healthy tissue. Scientists achieve this NIR absorption by synthesizing gold into specific nanostructures like gold nanoshells or gold nanorods. For gold nanorods, the absorption peak is shifted into the NIR region by adjusting the aspect ratio, or the rod’s length-to-width ratio.
Once the GNPs are concentrated in the tumor, a low-power NIR laser is directed at the area, causing the nanoparticles to heat up rapidly. This localized thermal energy raises the tumor temperature to the hyperthermia range, typically 40–45°C, which can sensitize cancer cells to other treatments. Alternatively, increasing the temperature above 50°C causes thermal ablation, leading to direct cancer cell death through coagulative necrosis.
Boosting Radiation and Imaging Effectiveness
Gold nanoparticles enhance two established clinical tools: radiation therapy and computed tomography (CT) imaging. In radiation therapy, GNPs act as radiosensitizers, increasing the effectiveness of X-ray treatment. Due to gold’s high atomic number (Z=79), it absorbs X-ray radiation far more efficiently than the lower-density elements found in biological tissue.
When irradiated, the GNPs absorb energy and emit a burst of low-energy secondary electrons in a process called the photoelectric effect. These highly reactive electrons travel only a short distance, depositing their energy directly into nearby cellular structures, including DNA, causing irreparable damage and cell death. By concentrating GNPs within the tumor, the local dose of radiation is amplified, maximizing tumor destruction while allowing for lower overall radiation doses that spare adjacent healthy tissue.
For diagnostics, gold nanoparticles serve as contrast agents for CT scans. Traditional CT imaging uses iodine-based agents, but gold’s much higher atomic number and electron density offer greater X-ray attenuation. GNPs have demonstrated a three-fold higher contrast than iodine agents, providing clearer visualization of tumor boundaries. Furthermore, their larger size gives them a longer circulation time in the bloodstream compared to small-molecule iodine agents, which extends the imaging window.
Clinical Status and Biocompatibility
The translation of gold nanoparticle therapies from the laboratory to patient care involves testing safety and efficacy. Several gold nanoparticle-based formulations have progressed into clinical trials for various applications, including thermal ablation and imaging enhancement. This progress is supported by the high biocompatibility of gold, which is chemically inert and does not readily react with biological components.
A major consideration for clinical adoption is the long-term fate of the nanoparticles within the body. While smaller, ultrafine gold nanoparticles (typically less than 5 nanometers in size) can be efficiently cleared through the kidneys and excreted in urine, larger particles present a challenge. Nanoparticles exceeding this size threshold are often taken up by the reticuloendothelial system, leading to their accumulation in organs such as the liver and spleen.
Long-term studies show that gold can persist in these organs for months or even years, raising concerns about chronic exposure and potential long-term toxicity. Overcoming this clearance hurdle and ensuring predictable, non-toxic excretion pathways are among the most significant regulatory challenges that must be addressed before gold nanoparticle technology can be widely integrated into standard cancer treatment protocols.