The use of nanoparticles to aid a drug’s effect is an important aspect of nanomedicine. Nanoparticles, when combined with drugs often improve a drug’s ability to reach its target, as in the case of doxorubicin, a treatment for cancer. The use of nanoparticles helps doxorubicin reach tumours, which allows the drug to exert its effect efficiently. The voyage of nanoparticles and their quest to improve and ensure is a fascinating tale. However, with events unfolding at a nanoscale, the story is rarely as straightforward as that.
On entering the human body, an average nanoparticle is exposed to a series of biological fluids and a of entities, though proteins constitute a majority. As the nanoparticle moves through various physiological compartments, it adsorbs layers of these entities it has come into contact with. This is referred to as the biomolecular corona. For the nanoparticle, its voyage entails not just the drug or therapy it carries, but also the so-called “baggage” of its journey. Therefore, when our trusted nanoparticle finally reaches the end of its journey, it is no longer a mere nanoparticle, but an entity coated with layers of biomolecular corona.
Our traveller puts on a new piece of clothing depending on the space he encounters. Each room consists of a different milieu, akin to the different biological compartments. He puts on layers of protein, lipids, sugars, etc. On reaching the target, the cellular machinery perceives the traveller based on the clothes he is clad in. In other words, the biomolecular corona serves as the identity of the nanoparticle for the cellular machinery.
This has a wide range of implications, including the cellular uptake of the nanoparticle and its effectiveness in bringing about the intended pharmacological effect. For the traveller aka our nanoparticle, the layers of clothing not only constitute an identity but also serve as a “memory” of the rooms he visited in the physiological space. For the nanoparticle, the biomolecular corona plays an important role in determining its recognition and, consequently, its fate.
One may think of an outer biomolecular corona as an impediment to the nanoparticle’s effectiveness by preventing it from exerting its full effect. While the outer layers may potentially hinder efficient activity in some cases, there have been studies that suggest that a biomolecular corona may in fact aid cellular uptake and minimise potential damage. The outer layers can minimize the potential toxicity of metallic nanoparticles and aid recognition, which ultimately plays a role in improved uptake.
In the world of, there have also been efforts to create stealth nanoparticles. These nanoparticles essentially minimise the layers a nanoparticle takes on, to prevent recognition. A stealth nanoparticle should ideally have little to no corona, thereby preventing an attack from the host’s cellular machinery. This can be achieved by modifying and functionalizing the nanoparticle surface, such as the use of polyethylene glycol as the surface functionalization. While this results in improved pharmacokinetics, many physicochemical factors such as radius of curvature and molecular weight are altered. Such modifications reduce the adsorption of entities however, some degree of corona formation seems inevitable.
It is, therefore, crucial to characterise a nanoparticle and study its interaction with human blood, serum, etc. Characterisation involves investigating the clothes or layers our nanoparticles is clad in. These serve as the means to understand its journey better as well as study its implications for the human body. Many techniques, such as differential centrifugal sedimentation, consider the layers of corona formed. More layers on a nanoparticle result in an increased sedimentation time. It is worth noting that while this technique can confirm the presence of a biomolecular corona, it does not help analyse the layers or the structure of the corona.
To distinguish between the contents of the hard and the soft corona is a challenge. A key aspect is also the in situ understanding of these complex dynamics as opposed to in-vivo models. This can prove to be especially tricky as nanoscale interactions occur in a highly dynamic time dependent manner. The exact implications of the layers of entities can be elusive to study as well.
Therefore, our nanoparticle and its quest are likely to be subjected to scientific curiosity and scrutiny for years to come.
References:
1) Breznica, P., Koliqi, R., & Daka, A. (2020). A review of the current understanding of nanoparticles protein corona composition. Medicine and pharmacy reports, 93(4), 342–350. https://doi.org/10.15386/mpr-1756
2) Durán, N., Silveira, C. P., Durán, M., & Martinez, D. S. T. (2015). Silver nanoparticle protein corona and toxicity: a mini-review. Journal of nanobiotechnology, 13, 1-17.
https://doi.org/10.1186/s12951-015-0114-4
3) Monopoli, M. P., Aberg, C., Salvati, A., & Dawson, K. A. (2020). Biomolecular coronas provide the biological identity of nanosized materials. Nano-Enabled Medical Applications, 205-229.
http://dx.doi.org/10.1038/nnano.2012.207
4) Barbalinardo, M., Bertacchini, J., Bergamini, L., Magarò, M. S., Ortolani, L., Sanson, A., Palumbo, C., Cavallini, M., & Gentili, D. (2021). Surface properties modulate protein corona formation and determine cellular uptake and cytotoxicity of silver nanoparticles. Nanoscale, 13(33), 14119-14129.
https://doi-org.salford.idm.oclc.org/10.1039/D0NR08259G
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Maitreyee Upadhye
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