Nanobiotechnology refers to the use of nanotechnology in biological applications, often as tools or therapeutic agents.
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As a relatively novel field, the terms nanobiotechnology, bionanotechnology, nanobiology, and others are used somewhat interchangeably.
Still, nanobiotechnology more specifically indicates the application of nanoscale materials to biological systems to serve a purpose or induce an effect, while bionanotechnology is the exploitation of biological materials that happen to be on the nanoscale.
For example, a nanobiotechnologist might synthesize lipid nanoparticles, functionalize them with drug cargo, then investigate the role of lipid nanoparticles in drug delivery. In contrast, a bionanotechnologist might synthesize a functional protein biomachine, then investigate its function and effects.
While these fields frequently overlap, nanobiotechnology is focused on providing biological and medical tools that can be utilized in research and the clinic as biosensors, therapeutic delivery agents, and biological manipulators.
How is Nanobiotechnology Producing Diagnostic Agents?
Nanomaterials are widely employed as in vivo and in vitro biosensors that offer significantly greater sensitivity than traditional small-molecule probes and dyes. During fluorescence microscopy, small molecule fluorophores with an affinity towards key cellular features, or that have otherwise been bound to molecules such as antibodies with high affinity towards the target site, are utilized to outline and identify cellular structures.
For example, the presence, size, and state of the nucleus can be interpreted in cell cultures by staining with fluorophores that bind proteins belonging to the nuclear envelope.
As discussed, there are many biological applications of nanobiotechnology that can offer significantly greater fluorescence intensity than small molecule reporters, either intrinsically, due to their much larger interaction cross-section with incident light, or by carrying multiple small molecule reporters on or within the nanoparticle simultaneously.
Intrinsically fluorescent nanomaterials are comparatively inert and non-interacting with surrounding biomolecules, thus offering improved stability and retention, and can be customized extensively with regards to their externally facing surface chemistry, providing an active targeting functionality.
Like small molecule fluorophores that can be directed to a target site by conjugation with antibodies or other specific biomolecule bonders, nanomaterials can be similarly bound with targeting molecules and thereby clearly identify features within the cell in vitro. This includes the plasma membrane or the whole body in vivo, such as tumor dimensions.
Cancer cells often over-express one or more protein receptors on the exterior surface of the cell, which can be made the target of such strategies. However, target specificity further extends to the level of the gene, where complementary DNA strands to the target can be bound to the nanoparticle surface. This level of specificity and sensitivity provides further application in the detection of sparse cells both in vivo and in vitro, for example, when identifying and separating stem cells from a culture in a high throughput manner by flow cytometry.
In this way, the unique properties and characteristics of nanoparticles can be exploited in a diverse range of diagnostic applications besides fluorescent microscopy. For example, the high density of iron or gold nanoparticles presents utility as X-ray and computed tomography contrast agents.
Magnetic nanoparticles such as those constructed from iron oxide can also act as powerful magnetic resonance imaging contrast agents for use in vivo and in vitro.
Here, the constituent protons of the particle align with an externally applied magnetic field and undergo short relaxation times that emit energy of a distinctive wavelength, allowing their precise location to be defined.
How is Nanobiotechnology Revolutionizing Drug Delivery?
Many small molecule drugs and diagnostic agents are poorly soluble and exhibit low retention time in the body, which can be improved by incorporation into a nanoparticle delivery system.
Nanoparticles are often coated with polyethylene glycol ligands that provide good solubility properties and prevent the accumulation of plasma proteins on the particle's surface, which would otherwise mark them for excretion via the hepatobiliary system.
Retention and circulation time are thereby improved, increasing the probability that the nanocarrier will reach the target site. As discussed, the highly customizable chemistry of the nanomaterial surface allows a wide variety of diagnostic and drug cargo to be loaded, providing a promising delivery platform with extreme specificity. In particular, any drug treatment producing significant side effects would benefit from transition to a nanomaterial delivery system, which has been explored extensively as a chemotherapeutic tool.
Most popularly, lipid nanoparticle-based delivery systems have reached the clinical stage and beyond, demonstrating good biocompatibility and the ability to merge directly with the cell membrane of target cells to deliver their cargo intracellularly. Those constructed from gold, iron oxide, and various polymers have also seen tentative use in the clinic.
Biomolecule therapeutic agents such as functional proteins and DNA or RNA strands are highly sensitive to degradation in the blood plasma. Many would not survive traversal to the target site without incorporation onto a nanomaterial delivery platform.
Protein therapy aims to introduce or enable the synthesis of beneficial proteins in the target cell by direct delivery of the protein or its precursors. For example, the recent mRNA-based COVID-19 vaccines utilized lipid nanoparticles to deliver mRNA strands instructing to transcribe the SARS-CoV-2 spike protein.
Gene modification technologies such as CRISPR also rely on the delivery of either the complete protein machinery or the relevant mRNA or DNA strands to initiate transcription once within the cell; liposomal formulations are utilized to deliver these materials to the cells being modified.
Gold nanoparticles have also been used to deliver the CRISPR-Cas9 system by firstly coating the surface of the particle with donor DNA followed by Cas9, and then covering this with positively charged polymer to protect the cargo and encourage passage into the net-negatively charged cytoplasm.
References and Further Reading
Fakruddin, M., et al. (2012). Prospects and applications of nanobiotechnology: a medical perspective. Journal of Nanobiotechnology. [Online]. 10(1). p. 31. https://jnanobiotechnology.biomedcentral.com/articles/10.1186/1477-3155-10-31
Wolfbeis, O. S. (2015). An overview of nanoparticles commonly used in fluorescent bioimaging. Chemical Society Reviews. [Online]. 44(14). pp. 4743–4768. https://pubs.rsc.org/en/content/articlehtml/2015/cs/c4cs00392f.
Korchinski, D. J., et al. (2015). Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue. Magnetic Resonance Insights. 8s1. p. MRI.S23557. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597836/.
Yip, B. (2020). Recent Advances in CRISPR/Cas9 Delivery Strategies. Biomolecules. 10(6). p. 839. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356196/.
Yu, M., et al. (2016). Nanotechnology for protein delivery: Overview and perspectives. Journal of Controlled Release. [Online]. 240. pp. 24–37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833694/.
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