Gold is one of our most valuable commodities but its use extends far beyond jewellery and gold bars. It’s a conductive material and is helping us to develop new medical innovations such as specialised patches that could be used to grow new heart tissue following a heart attack.

Heart attacks are caused by an abrupt blockage of one or more of the blood vessels that supply blood to the heart. This immediately reduces the supply of nutrients and oxygen to the heart muscle and if the blood flow is not restored quickly, causes irreversible death of the cells and eventually affects the performance of the heart muscle.

Unlike cells in the liver, heart cells can’t multiply. And although the heart contains few stem cells – “mother cells” that have the potential to become any type of cell in the body – their amount is not enough to repair the tissue damaged by a heart attack.

Because of this, the damaged tissue following a heart attack can become tough and fibrous and the efficiency of the heart to pump blood to the rest of the body is reduced. This eventually leads to end-stage heart failure, when treatment becomes difficult, and can lead to a patient’s death.

Currently the only therapeutic option available to treat patients with terminal end-stage heart failure is a heart transplant. However, the scarcity of cardiac donors has led to an urgent need to develop new experimental treatments.

One biomaterial that we’re working on to restore heart function is a special cardiac “patch” that utilises gold to help stimulate tissue growth.

These patches are three-dimensional biomaterials that work like temporary scaffolds to support cells and promote their reorganisation into functional tissue. After they are transplanted into the body, the patch integrates with the heart’s own tissue and improves its function.

Using gold to mimic ‘electrical wiring’

The heart can contract when electrical stimulation from one cell spreads to neighbouring cells. This allows the cells to beat and contract together, efficiently pumping blood to the rest of the body. For the patches to work we also need to mimic the native “electrical wiring” of the heart cells. This can trigger the cells to organise into functioning heart tissue that could be transplanted.

Most of the biomaterials that cardiac patches are made from are non-conductive. So the scaffold basically blocks electrical signals from travelling from one beating cell to neighbouring cells, making it extremely difficult to get them all to beat in unity.

In our work, we are using nano fibres covered with gold nano particles – the size of one billionth of a metre – to conduct the electrical signalling.

As the gold increases the connectivity of the engineered scaffold, cells grown on these scaffolds are also able to mature into functioning tissue, contracting with a greater force, rate and uniformity when compared to cells grown on other kinds of scaffolds.

This has all been done in a lab, but the next step is to test the potential of the engineered gold-incorporated scaffolds to restore heart function after a heart attack in an animal model. If successful, it will provide the first step to creating functioning, transplantable heart tissue that can eventually be used to treat human patients.

What is Nano-gold?

Nano-gold is a small object composed of gold and, which has one-, two-, or three-dimensions on the nanoscale, i.e., a sheet, a rod, or a particle. For the purpose of our discussion nano-gold refers to the gold moiety alone, while nano-construct infers a moiety that consists of a core of nano-gold to which has been adsorbed or covalently bound a biomolecule or xenobiotic (drug, therapeutic, analytic), forming a more or less defined overall structure. A nano-gold construct formulation defines the character and often the proportions of bound entities to the nanoscale gold core.

Whether biomolecules or drugs bound physically or chemically to the gold surface should be considered when evaluating the size of a nano-construct seems to be somewhat dependent on the technology being used. For example, electron microscopy can readily detect the high-contrast gold core of a nanoconstruct, but it is much more difficult to visualize or measure exactly what and how many biological molecule or xenobiotic might be bound. On the other hand, dynamic light scattering is due to the entire entity, and all or most of the bound elements are included in the measurements. Thus, there are many challenges even at the level of rigorously defining what exactly we mean by nano-gold or a nano-gold therapeutic. Hopefully, these introductory comments and brief definitions have armed the novice to nano-gold with information to navigate our orientation to recent discoveries of exciting new roles for nano-gold in nanomedicine.

Properties of Nano-Gold In Vivo

When administered systemically, it is not surprising that gold nano-constructs are readily taken up by the reticulo-endothelial system including Kupffer cells in the liver [3]. While local presentation such as intra-tumor injection appears to result in retention of the nano-constructs [14]. Similarly, treatment of the cornea appears to result in an initial local distribution, followed by slow clearance and was not associated with inflammation or edema (in a rabbit study), and was effective in delivering gene transfer [7].

Nano-Gold in Energy Transfer for Therapeutics and Diagnostics

Nano-gold also has physical properties that make it useful across a range of other applications. Both optical and plasmon resonance properties suggest that they will have multiple applications across both therapeutics and diagnostics [15]. Used in conjunction with X-radiation, smaller nano-gold constructs appear to be effective in raising intracellular free radical concentrations [16], providing another potential mechanism via which cancer cells might be eliminated. Using related technology, X-ray computed tomography, targeted nano-gold labeled cells were readily detected in a small animal model of human disease [17], adding to the potential diagnostic arsenal.

Conclusion

Evidence in support of nano-gold constructs as bases for multiple medical applications appears to be accumulating with generally favorable outcomes to date. There is still much to learn about the potential cytotoxicity, which at least initially appears to be minimal at effective doses. The binding of biomolecules appears to be another area for further study and the general area of specific tissue and/or cellular targeting is a broader issue for all of nano-medicine and medicine generally. Nano-gold may provide a new light for applications spanning from gene-regulation to diagnostic imaging. Although the light is yet a single candle, the studies summarized in this virtual edition point the way to greater illumination of nano-gold in medicine.

References

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16. Misawa M, Takahashi J: Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations. Nanomedicine: Nanotechnology, Biology and Medicine 2011; 7(5): 604-614