Small Molecules that Make a Big Difference: Medical Applications of Nanoparticle Engineering

By: Emily Bush

The study of cellular biology has widespread applications and implications in the medical world, and one area garnering increasing attention in modern research is that of nanoparticles. Nanoparticles, or small molecules of 1-100 nanometers in size, can range from naturally occurring biological molecules to lab-engineered proteins. Though these nanoparticles are not naturally synthesized by the human body, the overlap between proteomics and artificial intelligence is a rapidly developing field that promises applications in biochemistry, medicine, archeology, forensics, and more. 

Although nanoscience has been applied in a variety of fields, the most promising recent developments in the field point towards applications in medicine. Nanopharmaceuticals for drug delivery have become more prevalent on the market, and recently the area of bio-diagnosis and cancer therapy using nanoparticles has received increasing attention in the research community (Wang & Wang, 2014). Specific properties of nanoparticles point to great potential for their role in drug delivery, including their ability to “enhance'' chemical reactions within cells to trigger biological effects as well as their “increased residence time and exposure” in cellular environments (Verma et al., 2018). Traditional cancer treatment drugs require high doses due to lack of bio-accessibility and thus trigger harmful and severe side effects, an issue that can be mitigated with the use of nanoparticle carriers. In photodynamic cancer therapy specifically, atomic oxygen is transported within dye molecules to trigger cancer cell death. Traditionally, these dye molecules will also spread to healthy cells in the body. Using nanoparticle carriers, however, limits the spread of these dye molecules within cancerous cells and thus reduces harmful side effects such as increased sensitivity to light (Salata, 2004). Overall, maximizing the potential of nanoparticles to precisely deliver medications into target cells and tissues can lead to a plethora of future achievements in cancer therapy. 

More recently, researchers have also been applying nanoparticle properties to the development of a more effective COVID vaccine. Currently approved vaccines, including mRNA based ones, consist of natural proteins and function by introducing the spike of the coronavirus molecule into the immune system without a functional coronavirus. However, the receptor-binding domain (RBD) of the molecule can often be hidden by other surface proteins in current vaccines, leading to decreased efficacy and higher potential side effects (Jacobsen, 2021). When a nanoparticle protein is engineered to feature only the critical RBD portion of the molecule, however, researchers have seen an immune response ten times more effective in neutralizing the propagation of the virus throughout the body (Jacobsen, 2021). In essence, the ability to replicate this specific region of the virus means that it can be more fully exposed to the immune system and translates to a much higher probability that the body will develop the proper antibodies against it. Furthermore, this form of protein engineering involves the study of protein folding, and thus can potentially be applied to the mitigation of other diseases that involve misshapen proteins, such as Alzheimer’s or Huntington’s disease (Jacobsen, 2021).

Looking forward, protein design presents many promising applications in the medical world, but the mystery and complexity of protein folding is still a large hurdle to overcome for further advancements in proteomics and nanoparticle engineering (Jacobsen, 2021). Protein labs in recent years have made gradual improvement in predicting protein structure through human-driven experiments, but success rates are still low in this area. On the other hand, a new approach has been practiced in recent years through a more interdisciplinary method, enlisting the help of artificial intelligence. DeepMind, an offshoot of Google AI, has created an artificial intelligence program called AlphaFold which has been able to predict protein structures and amino acid sequences up to four times more accurately than any leading protein engineering lab today (Jacobsen, 2021). Depending on the complexity of the protein in question, the program’s predictions were at times near replicas of those determined using the most reliable lab-based methods such as X-ray crystallography and cryo-EM (Callaway, 2021). Going forward, the use of technology such as AlphaFold can generate a vast amount of genomic data and translate this into structures, opening the door for a flourishing field of protein analysis that can be applied to any field that involves proteomics. DeepMind plans to make this program available so that scientists can employ the tool for use in their own research labs and accelerate protein research greatly to expand nanoparticle and proteomic research. In conclusion, the joint growth of proteomics and nanoparticle research has shown promising results in the pursuit of improved drug delivery, vaccine development, and protein analysis. The advances made in protein structure analysis through its intersection with artificial intelligence also clearly establishes the efficacy of collaborative and interdisciplinary growth. With this integrative approach, nanoparticle and protein engineering has great potential to address cancers and diseases that involve protein misfolding, generating solutions to long-studied medical complexities.

Figure 1. This image shows how a nanoparticle can be used in drug transport and cancer therapy by allowing hydrophobic molecules to enter the lipid bilayer and into the cell. 

Figure 2. This image shows a side-by-side comparison of the COVID virus along with the structure and appearance of the protein nanoparticle vaccine. This picture effectively demonstrates the complexity of the nanoparticle vaccine and the different spike structures it delivers into the body to boost the immune response beyond a normal vaccine.

References

Callaway, E. (2020). “It Will Change Everything”: AI Makes Gigantic Leap in Solving Protein Structures. Springer Nature Limited. https://media.nature.com/original/magazine-assets/d41586-020-03348-4/d41586-020-03348-4.pdf

Jacobsen, R. (2021). Artificial Proteins Never Seen in the Natural World Are Becoming New COVID Vaccines and Medicines. Scientific American, 324. https://www.scientificamerican.com/article/artificial-proteins-never-seen-in-the-natural-world-are-becoming-new-covid-vaccines-and-medicines/

Murthy S. K. (2007). Nanoparticles in modern medicine: state of the art and future challenges. International journal of nanomedicine, 2(2), 129–141. 

Salata, O. V. (2004, April 30). Applications of nanoparticles in biology and medicine. Journal of Nanobiotechnology. Retrieved October 11, 2021, from https://jnanobiotechnology.biomedcentral.com/articles/10.1186/1477-3155-2-3. 

Verma, D., Gulati, N., Kaul, S., Mukherjee, S., & Nagaich, U. (2018). Protein Based Nanostructures for Drug Delivery. Journal of pharmaceutics, 2018, 9285854. https://doi.org/10.1155/2018/9285854

Wang, E. C., & Wang, A. Z. (2014). Nanoparticles and their applications in cell and molecular biology. Integrative biology : quantitative biosciences from nano to macro, 6(1), 9–26. https://doi.org/10.1039/c3ib40165k

Images

Nanoparticle vaccine for COVID-19 spurs robust immune response in preclinical tests. (2021, Spring). [Illustration]. https://www.scripps.edu/news-and-events/press-room/2020/20200921-zhu-covid19.html

Hong, S., Choi, D. W., Kim, H. N., Park, C. G., Lee, W., & Park, H. H. (2020). Protein-Based Nanoparticles as Drug Delivery Systems. Pharmaceutics, 12(7), 604. MDPI AG. Retrieved from http://dx.doi.org/10.3390/pharmaceutics12070604