Gold has been used in medicine for decades, most prominently as an injectable and oral treatment for rheumatoid arthritis, and its medical footprint has expanded considerably in recent years. Ionic gold compounds have roughly seventy years of clinical history behind them, while gold nanoparticles are now being explored for everything from cancer therapy to rapid diagnostic tests and drug delivery. The story of gold in medicine is not one single application but a surprisingly broad portfolio spanning old-school pharmacology and frontier nanotechnology.
Gold Compounds for Rheumatoid Arthritis
The longest-running medical use of gold is in treating rheumatoid arthritis, a practice sometimes called chrysotherapy (from the Greek word for gold). Injectable gold salts like gold sodium thiomalate were introduced in the early twentieth century and remained a standard treatment for active rheumatoid arthritis for decades. In a controlled trial comparing injectable gold sodium thiomalate, oral auranofin, and placebo, both gold treatments outperformed placebo on measures like the number of painful joints, physician-assessed disease activity, and markers of inflammation. Injectable gold tended to work somewhat better, but the oral form caused fewer side effects.1PubMed. Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial
Auranofin, the oral gold compound approved by the FDA in 1985, was a significant step because it let patients take gold therapy as a pill rather than needing regular injections. In early studies, patients taking auranofin showed drops in inflammatory markers and rheumatoid factor levels, along with meaningful reductions in joint swelling over the course of several months.2PubMed Central. Auranofin. New oral gold compound for treatment of rheumatoid arthritis A Cochrane systematic review later concluded that auranofin provides a real but modest benefit for rheumatoid arthritis disease activity, though it is less effective than methotrexate or injectable gold.3Cochrane Database of Systematic Reviews. Auranofin for rheumatoid arthritis
In practice, gold therapy for arthritis has largely been sidelined by newer drugs, especially methotrexate and biologic agents that target specific immune pathways. But auranofin never disappeared entirely. It remains FDA-approved, and its established safety profile has made it an attractive candidate for repurposing in other diseases, which has given this old drug a surprising second act.
Repurposing Auranofin Beyond Arthritis
Researchers noticed that auranofin’s mechanism of action, specifically its ability to inhibit an enzyme called thioredoxin reductase, could be useful far beyond inflamed joints. Thioredoxin reductase helps cells manage oxidative stress, and certain cancer cells and parasites depend heavily on this enzyme to survive. That vulnerability has opened two distinct lines of research.
Cancer Applications
In cancer research, auranofin has drawn attention for its potential to kill tumor cells that resist conventional chemotherapy. Laboratory studies found that cisplatin-resistant ovarian cancer cells overexpress thioredoxin reductase, and auranofin’s targeted inhibition of that enzyme triggered cell death in those resistant cells.4PubMed. Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells Follow-up work confirmed that thioredoxin reductase inhibition is genuinely the drug’s primary mechanism, not a secondary effect.5PubMed. Repurposing of auranofin: Thioredoxin reductase remains a primary target of the drug These are still preclinical findings, and auranofin has not been approved for any cancer indication. But because the drug is already FDA-approved for another condition and has known pharmacology and side-effect profiles, the path from laboratory to clinical testing is shorter than it would be for a completely new molecule.
Parasitic Infections
Through high-throughput screening efforts funded by the National Institutes of Health, auranofin was identified as active against Entamoeba histolytica and Giardia, two parasites that cause diarrheal disease worldwide.6PubMed Central. Reprofiled drug targets ancient protozoans: drug discovery for parasitic diarrheal diseases The drug worked against both standard and metronidazole-resistant strains of Giardia, which matters because metronidazole is the usual first-line treatment and resistance is a growing concern. A phase I clinical trial in healthy volunteers confirmed that auranofin doses relevant for antiparasitic use were well tolerated, clearing a necessary early hurdle for potential future use in infected patients.7PubMed Central. Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent Again, the target turned out to be the same enzyme, thioredoxin reductase, which E. histolytica relies on to neutralize the oxidative assault from the human immune system.
Gold Nanoparticles in Cancer Treatment
While auranofin is a molecular gold compound, gold nanoparticles are a fundamentally different class of medical tool. These are tiny structures, typically between one and a hundred nanometers, engineered to exploit gold’s unusual behavior at the nanoscale. One of the most studied applications is photothermal therapy, sometimes called photoablation. Gold nanoparticles absorb light at specific wavelengths and convert it into heat. When the particles accumulate inside a tumor, a clinician can shine near-infrared light on the area and essentially cook the cancer cells from within, while leaving surrounding tissue largely intact.8PubMed Central. Gold Nanoparticles for Photothermal Cancer Therapy By tweaking the shape and size of the nanoparticles, researchers can tune which wavelengths of light they respond to, including near-infrared wavelengths that penetrate deeper into tissue.
A separate but complementary approach uses gold nanoparticles as radiosensitizers, meaning they make tumors more vulnerable to standard radiation therapy. When gold nanoparticles concentrate inside a tumor, they enhance the local effect of radiation, potentially allowing lower radiation doses to achieve the same tumor-killing result, or better results at the same dose. The mechanism was initially thought to be purely physical: gold’s high atomic number causes more radiation energy to be deposited locally. More recent research suggests the picture is more complex, with chemical and biological effects also playing important roles.9PubMed Central. Gold Nanoparticles as a Potent Radiosensitizer: A Transdisciplinary Approach from Physics to Patient What makes this approach particularly appealing is that the same nanoparticles that boost radiation therapy can also serve as contrast agents for medical imaging, letting doctors both visualize and treat a tumor with one platform.10PubMed Central. Gold nanoparticles in radiation research: potential applications for imaging and radiosensitization
Achieving all of this requires sophisticated surface engineering. Gold nanoparticles used in medicine are typically coated with specialized molecules that help them circulate in the bloodstream long enough to reach the tumor, attach to cancer cells selectively, and carry therapeutic payloads if needed. The complexity of this surface modification is one of the reasons gold nanoparticle therapies are still mostly in preclinical and early clinical testing rather than routine use.11PubMed. Gold nanoparticle surface functionalization: a necessary requirement in the development of novel nanotherapeutics
Diagnostic Uses You Have Probably Already Encountered
If you have ever used a home pregnancy test or a rapid COVID-19 antigen test, you have already held gold nanoparticles in your hand. The colored line that appears on these lateral flow assay strips is typically produced by gold nanoparticles attached to antibodies. When the target molecule (a hormone, a viral protein, or another biomarker) is present in the sample, it gets sandwiched between antibodies, and the gold nanoparticles cluster together to produce a visible color change, usually a red or pink line.
During the COVID-19 pandemic, gold nanoparticle-based lateral flow assays became one of the most widely deployed rapid diagnostic tools in history, valued for their ability to deliver results at the bedside without laboratory equipment.12PubMed Central. Gold Nanoparticle-Mediated Lateral Flow Assays for Detection of Host Antibodies and COVID-19 Proteins The same basic technology is used for a wide range of other infections and conditions. Researchers have developed signal-enhanced versions using dual gold nanoparticle conjugates that can detect hepatitis B surface antigen with higher sensitivity than conventional single-nanoparticle designs, without adding extra steps for the user.13ACS Omega. Signal-Enhanced Lateral Flow Immunoassay with Dual Gold Nanoparticle Conjugates for the Detection of Hepatitis B Surface Antigen
Beyond simple test strips, gold nanoparticles are being developed as contrast agents for advanced cancer imaging techniques. Their optical and electronic properties make them versatile platforms that can enhance computed tomography (CT) scans, photoacoustic imaging, and other modalities, helping doctors locate tumors with greater precision.14PubMed Central. Recent Development of Gold Nanoparticles as Contrast Agents for Cancer Diagnosis Gold nanostructures are also used in a technique called surface-enhanced Raman spectroscopy, or SERS, which can detect biological molecules with extremely high sensitivity. SERS-based biosensors built around gold nanostructures can identify specific proteins, nucleic acids, and other biomarkers, potentially enabling earlier disease detection.15PubMed Central. Biosensing Using SERS Active Gold Nanostructures
Gold Against Drug-Resistant Bacteria
Antibiotic resistance is one of the most pressing public health threats of the twenty-first century, and gold nanoparticles have shown some early promise as an alternative antibacterial strategy. By functionalizing gold nanoparticles with specific surface groups, researchers have created particles that kill both Gram-negative and Gram-positive bacteria, including multi-drug-resistant strains that cause urinary tract infections. In laboratory tests, these nanoparticles showed low toxicity to mammalian cells, and bacteria did not develop resistance even after twenty generations of exposure.16PubMed Central. Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria That last point is encouraging because the rapid emergence of resistance is what makes conventional antibiotics lose effectiveness over time. The research on antibacterial gold nanoparticles is still in the laboratory stage, but the fact that resistance did not emerge easily in early experiments has kept the field moving forward.17PubMed Central. Gold Nanoparticles: Can They Be the Next Magic Bullet for Multidrug-Resistant Bacteria?
What Happens to Gold Nanoparticles Inside the Body
A major question hanging over all nanoparticle-based medicine is what happens to the particles after they do their job. Gold is chemically inert, which is one reason it appeals to biomedical researchers. But “inert” does not mean “invisible to the body.” When gold nanoparticles are injected intravenously, they tend to accumulate in the liver and spleen, and they can persist there for a long time.
In one animal study, PEG-coated gold nanoparticles remained in the liver and spleen for at least 28 days after a single injection. Early time points showed signs of liver cell stress and spleen changes, which resolved within a month, but later time points revealed shifts in lipid metabolism and liver-injury markers that, while not dramatic, flagged the possibility of lingering effects from long-term tissue accumulation.18PubMed Central. Pharmacokinetics, Biodistribution, and Biosafety of PEGylated Gold Nanoparticles In Vivo Another study using PEG-coated hollow gold nanospheres found that gold levels in the liver, spleen, kidney, and muscle dropped by roughly 30 to 45 percent between day 14 and day 90 after injection, indicating slow but incomplete clearance.19PubMed Central. Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow gold nanospheres
More concerning findings came from a longer-term study tracking BSA-coated gold nanoparticles out to 120 days. Instead of steadily declining, gold concentrations in the spleen and kidneys actually increased over time, with a 53 percent rise in the spleen and a 150 percent rise in the kidneys compared to day one. The biological effects included early inflammatory and fibrotic responses, most pronounced in the kidneys despite relatively small amounts of gold accumulating there.20PubMed Central. Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys The surface coating, size, shape, and dose of the nanoparticles all influence where they end up and what they do once they are there, which is why safety data from one type of gold nanoparticle cannot be casually applied to another.
How Far Along Are Clinical Trials
Given how much laboratory research exists on gold nanoparticles, a reasonable question is: how close is any of this to actual patient care? The honest answer is that gold nanoparticle medicine is still in early translation. A review of clinical trials found over twenty studies focused on gold nanoparticle safety in humans, employing the particles as drug delivery vehicles, for photothermal therapy, and for their intrinsic therapeutic effects through various routes of delivery. The studies revealed no major safety concerns, but the total number of trials and enrolled patients remains small.21ScienceDirect. Applications and safety of gold nanoparticles as therapeutic devices in clinical trials
The gap between exciting preclinical results and routine clinical use is wide for gold nanoparticles, as it is for most nanomedicines. Manufacturing challenges are significant: producing nanoparticles with consistent size, shape, and surface chemistry at scale is harder than making a conventional drug. Regulatory frameworks were not originally designed for materials that blur the line between drug and device. And long-term safety data in humans is still thin, particularly regarding what happens when gold nanoparticles accumulate in organs over months or years.
Emerging Frontiers in Gold-Based Imaging
A particularly exciting area of current research involves gold nanoclusters, which are even smaller than standard nanoparticles, typically fewer than a couple of hundred atoms. At this scale, gold begins to exhibit fluorescent properties. Gold nanoclusters can emit light when excited, resist photobleaching better than many conventional fluorescent dyes, and are generally considered biocompatible, making them promising candidates for biological imaging.22PubMed Central. Advances of gold nanoclusters for bioimaging
Researchers are engineering these nanoclusters to emit in what is called the second near-infrared window, wavelengths between about 1000 and 1700 nanometers. Light in this range penetrates deeper into living tissue and produces less background noise from the tissue itself than shorter wavelengths. This means that gold nanocluster-based contrast agents could allow real-time imaging inside living organisms with higher spatial resolution and deeper tissue penetration than current optical methods, enabling doctors to watch disease progression and treatment responses as they happen.23Chemical & Biomedical Imaging. Gold Nanoclusters as High Resolution NIR-II Theranostic Agents The work is still preclinical, but it represents a direction that could eventually change how surgeons visualize tumor margins during operations or how oncologists monitor treatment without repeated biopsies.
Gold Nanoparticles and the Brain
Neurological diseases present unique drug delivery challenges because the blood-brain barrier blocks most substances from entering brain tissue. Gold nanoparticles, when engineered with the right surface chemistry, may be small and versatile enough to cross this barrier. Preclinical research has explored their use in Alzheimer’s disease, Parkinson’s disease, and stroke, focusing on their potential to provide neuroprotection and reduce neuroinflammation. Cellular and animal models have shown promising results across multiple pathways, though human studies are still a long way off.24PubMed Central. Gold Nanoparticles in Neurological Diseases: A Review of Neuroprotection Neurodegenerative disease applications remain speculative compared to gold’s more established roles in rheumatology and diagnostics, but the ability to functionalize gold nanoparticles for brain-targeted delivery keeps them on the research agenda.
Making Gold Nanoparticles Without Harsh Chemicals
Traditional methods for synthesizing gold nanoparticles often involve chemical reducing agents that can be toxic and generate hazardous waste, which is ironic for materials intended for biomedical use. A growing body of work focuses on “green synthesis” approaches that use plant extracts, microorganisms, or other biological materials as reducing agents instead. These methods are considered more environmentally friendly, potentially cheaper, and may produce nanoparticles with inherently better biocompatibility because the biological capping agents are less toxic than their chemical counterparts.25PubMed Central. Plant-Based Synthesis of Gold Nanoparticles and Theranostic Applications: A Review26PubMed Central. Gold Nanoparticles: Biosynthesis and Potential of Biomedical Application
Green synthesis is not just an environmental nicety. If gold nanoparticle-based therapies ever reach large-scale manufacturing, the synthesis method will matter for cost, reproducibility, and regulatory approval. Whether plant-based synthesis can achieve the consistency needed for pharmaceutical-grade nanoparticles at scale remains an open question, but it reflects a field that is already thinking about practical manufacturing hurdles alongside the basic science.