The use of nanotechnology in medicine is one of the most exciting advancements right now for both diagnostics and treatments. Nanomedicine is defined as the use of nanoscale technology for medical applications, such as drug delivery, imaging and diagnostics. This can be in the form of nanocarriers, which utilize particles that are 1-100 nm in size, such as polymeric carriers, dendrimers, or liposomes that transport drugs to specific areas.
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The use of nanoscale materials and particles enables more natural interaction with other body cells due to the similarity in size. While there is research investigating the significance of nanoparticle use for delivering chemotherapy drugs, an international research group has focused on this novel application to transport non-opioid drugs into nerves for pain relief.
Using nanotechnology for pain relief
Nanoparticle drug encapsulation provides a promising future for medicine; the nanoscale size of these carriers ensures movement across challenging barriers for drugs that would usually be too large. The functionalization of these particles enables precise targeting of the drugs to the areas of concern, reducing the overall toxicity to neighboring healthy cells.
The enhanced permeability and retention effect enables nanoparticles to accumulate in tumor tissue more readily than healthy tissue due to the leaky vasculature and decreased lymphatic drainage. The high precision benefit of nanoparticle use has increased research into the nanocarrier application for toxic chemotherapy drugs. This would enhance chemotherapy treatment efficacy due to providing a precise target for the drugs, decreasing drug dosages, and increasing cancer patients' quality of life.
The precise targeting potential of these particles enables them to have limitless applications within medicine. While targeting cancer is a very significant advantage, other benefits also include pain-relieving therapies.
A nanoparticle-based approach to targeting and providing pain relief would be a significant alternative to opioid therapy, which would not only help address and decrease the opioid epidemic but also provide a more precise method of targeting pain for chronic sufferers.
The dangers of opioid therapy for pain relief
Opioids are a class of highly addictive analgesic drugs, and, while they may provide powerful pain relief, the side effect is usually detrimental to patient health. A review that looked at the comparative effectiveness of opioid therapy for chronic pain found that the use of opioids for short-term use was not superior to the benefits of non-opioid treatment, but held more harm.
However, the effects of long-term use of opioids were dose-dependent. The dopamine center of the brain that pain-relieving drugs target requires higher doses for long-term pain relief due to the gradual decrease in efficacy. Combined with the addictive nature of opioid drugs, they are no longer seen as being a viable option for pain relief.
A novel pain-relieving treatment
A team of international researchers led by Dr. Nigel Bunett, and published in Nature Nanotechnology, found a novel method of targeting nerve cells that would provide a safer and more competitive alternative to opioid therapy for pain relief. By utilizing the versatile nature of nanoparticles, they were able to target receptors within endosomes which are usually activated to cause pain.
G-coupled protein receptors
It was thought that G-coupled protein receptors functioned at the surface of nerve cells. However, Bunett’s team found that these key pain receptors actually work within the endosome once activated.
The research group focused on the neurokinin-1 receptor, for which an FDA-approved drug already exists. Unfortunately, due to drugs targeting surface receptors and not receptors that work within the endosome, the approved drug was not able to effectively block the neurokinin-1 receptor.
With the novel application of nanoparticles, this issue could now be addressed, and the team of international researchers worked to target these key pain receptors, previously unattainable due to being protectively enveloped within the endosome.
Nanoparticles for targeting endosomes
The researchers were able to encapsulate the neurokinin-1 receptor blocker within nanoparticles to deliver drugs into the endosome.
The endosomes hold activated neurokinin-1 receptors and activate spinal neurons which cause pain. However, due to the minuscule size of nanoparticles, they are able to travel into endosomes, where the drug can be released to inhibit the activation of the spinal neurons, resulting in pain relief.
pH-sensitive nanoparticles were used due to the acidification of intracellular compartments such as endosomes which would ensure the breakdown of the nanoparticles and enable drug release.
Benefits of using nanoparticles for pain relief
This novel treatment has induced a sustained and more complete anti-nociception in preclinical models compared to conventional therapies, including opioid therapy.
The use of nanoparticles ensures a more targeted approach to pain, such as through targeting receptors within endosomes. This subsequently allows lower dosages of drugs to be used, which is a cheaper and more sustainable therapy for patients and healthcare systems.
Further studies would be required before nanoparticle-encapsulated analgesics can be advanced to clinical trials, including toxicology assays. However, this advancement in a higher targeted pain-relieving approach would be beneficial for chronic pain sufferers.
The research group suggests therapeutic efficacy could be improved through combining antagonists of different G-coupled protein receptors into the same nanoparticle to co-mediate pain transmission, delivering drugs to select pain-transmitting neurons.
This would advance the treatment of pain towards a more personalized approach instead of relying on drugs that have a more broad-spectrum effect. This would enhance the quality of patient care and quality of life.
References
- Ramírez-García P, Retamal J, Shenoy P, Imlach W, Sykes M, Truong N et al. A pH-responsive nanoparticle targets the neurokinin 1 receptor in endosomes to prevent chronic pain. Nature Nanotechnology [Internet]. 2019 [cited 31 March 2021];14(12):1150-1159. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765343/
- Chou, R., Hartung, D., Turner, J., Blazina, I., Chan, B., Levander, X., McDonagh, M., Selph, S., Fu, R., & Pappas, M. (2020). Opioid Treatments for Chronic Pain. Agency for Healthcare Research and Quality (US). Available at: Opioid Treatments for Chronic Pain [Internet] - PubMed (nih.gov)
- Senapati S, Mahanta A, Kumar S, Maiti P. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduction and Targeted Therapy [Internet]. 2018 [cited 31 March 2021];3(1). Available from: https://www.nature.com/articles/s41392-017-0004-3
Further Reading
Nanotechnology's triple threat: Advancing precision cancer treatment