When we think about gold, the first thing that usually comes to mind is jewelry, possibly followed by coins and ingots. Aside from its economic and ornamental value, the precious metal also has many other scientific and medical applications.
Humans have been using gold in medicine for at least 3,000 years. Ancient Egyptians used gold in potions and elixirs for purification, while traditional Chinese medicine used the metal to create acupuncture needles. In the medieval era, gold dentures became widespread as well.
The potential for using gold in oncology and imaging fields has been an area of interest since the 1970s. Nanotechnology is a hotbed for innovation right now, with numerous studies looking at the impact of gold nanoparticles on the human body.
A recent study conducted by a team of researchers at the National University of Singapore (NUS) is worth a look at in this context. Published in the November 2024 edition of Advanced Functional Materials, it explains some highly innovative approaches to targeted drug delivery.
Experimenting with Different Shapes and Sizes of Nanoparticles
A nanoparticle is any particle whose size can be measured in the nanoscale, between 1 and 100 nanometers. For reference, one nanometer is about 100,000 times smaller than the width of a human hair. Nanoparticles can be made from both elements (like gold and silver) and compounds.
The NUS study involves elemental nanoparticles created from pure gold. Nanoparticles can have various sizes and shapes, depending on the lab conditions and chemicals used in the growth process. And the shape of the particle can define how the particle behaves inside the body.
For the purpose of the study, the team from the Department of Biomedical Engineering at NUS experimented with six different shapes and dimensions. They included three shapes – rod, triangle, and sphere – at two sizes each of 40nm and 80nm.
Nanoparticles can behave in myriad ways once they are injected into the cellular environment. For the purpose of comparison and measurements, the team needed a way to make all the nanoparticles target the same tumor cell types.
To facilitate this, researchers tagged all nanoparticles with DNA barcodes. They serve a dual purpose, allowing the nanoparticles to zero in on specific cells, while also ensuring that the researchers can track their whereabouts inside the body.
The DNA barcodes were securely anchored to the gold nanoparticles using a process called thiol functionalization. Thiols are a family of organic compounds that have a strong affinity for binding to the surfaces of metals like gold and silver.
While one of the thiol molecules (ligand) is securely anchored to the gold particle, the other end contains the DNA sequence label. Thiol functionalization is a reliable method for ensuring that the DNA barcodes are securely anchored and protected from enzymatic degradation inside the body.
Key Findings of the NUS Study Regarding Spherical Nanoparticles
A cursory review of various experiments and studies involving nanoparticles for drug delivery shows a preference for one specific shape – the sphere. The vast majority of FDA-approved nanoparticle drug mechanisms use spherical particles, and for good reason.
The spherical shape is incredibly stable and less likely to degrade over time, compared to others like rods and cubes. It has an excellent ability to evade immune clearance systems, ensuring a longer presence in the bloodstream.
Spherical shapes also offer a higher surface-area-to-volume ratio, meaning you can efficiently carry more drug molecules and also ensure a controlled release of drugs. Due to the many inherent advantages of the shape, spherical nanoparticles are considered the gold standard for targeted drug delivery systems.
The NUS study confirms some of the established properties of spherical nanoparticles, while also raising some other possibilities. For instance, the team discovered that sphere shape allowed nanoparticles to easily evade the immune system in living bodies (in vivo).
However, the shape fared poorly in lab cell culture trials (in vitro). This raises an important point that future experiments involving spherical particles will have to take into account. Overall, the findings indicate that spherical shapes are ideally suited for targeted drug delivery to tumor cells.
Alternatives Also Exist in the Form of Triangular Nanoparticles
Perhaps the most important finding of the study was the viability of other shapes besides spheres for cancer treatment. Of the two remaining shapes, the triangle held the most promise, that too with a significant advantage over the sphere in one area.
While spheres fared poorly in in-vitro tests, triangular gold nanoparticles were equally adept at reaching the targeted cancer cells in both in vitro and in vivo tests. The particles also had excellent photothermal properties, meaning they could efficiently absorb light radiation and convert it into heat.
This is good news from a therapeutic standpoint, as light-absorbing nanoparticles can be used to destroy targeted cancer cells using heat energy, without causing any damage to healthy cells. The process, which uses infrared lasers, is called photothermal cancer therapy.
Reasons Why Nanoparticles are Superior for Cancer Drug Delivery
Traditional chemotherapy drugs are very good at killing cells. Unfortunately, we lack efficient targeting systems to ensure that these drugs only wreak havoc on cancer cells. Many of the drugs also lack water solubility and stability, which can severely degrade their overall bioavailability.
Frequent doses are required to overcome these deficits, increasing the risk of exposure to healthy cells in the body. Gold nanoparticles offer a clear upgrade over traditional drug delivery options (oral tablets, IV infusions, injections, topical applications).
DNA-tagged gold nanoparticles have proven their effectiveness in reducing the severity of side effects through accurate targeting of cancer cells. Higher bioavailability and stability also mean doctors can achieve results with fewer doses, further reducing the risk of side effects.
Apart from delivering drug molecules, nanoparticles in exotic shapes can also be used to safely burn off cancer cells using infrared lasers. The NUS team has plans to expand their library of nanoparticle shapes and explore the viability of using the photothermal therapy to treat breast cancer.
