By Sarah, Fall 2022.
Humankind has had its eyes on the microscopic world for centuries since Jonathan Swift illustrated the fantastically tiny world of the Lilliputians in his classic novel, Gulliver’s Travels. Yet, popular interest in the smaller-scale extends beyond fairy tales. Scientists have been fascinated with the microscopic for as long as humans have looked to the stars or the ocean’s depths. Recent decades saw a rise in scientific interest for nanotechnology, with the emergence of promising new advancements and applications. As more clinical intersections between the life sciences and nanotechnology emerged, such as tissue engineering projects and cell repair, nanomedicine cemented itself as a valuable and significant interdisciplinary subfield.
Renowned theoretical physicist Richard Feynman pioneered the concept of synthesizing materials through direct atomic manipulation and control, which inspired the nanotechnology discipline in the early 1960s. The intersection of physics, chemistry, biology, and engineering has led to the development of many biodiagnostic tools. One of the most widely used technologies in nanomedicine is the use of microfluidic biosensors, which are colloquially referred to as the “lab-on-a-chip”. Microfluidics involves precise control and manipulation of extremely small amounts of solution, using capillary flow or active micropumps or microvalves. The fabrication and medical application of these sensors was so successful that scientists ventured to further reduce the size of these platforms.These biosensor platforms have been extremely successful in immunodiagnostic research; companies have taken advantage of microfluidics to replicate physiological environments pertinent to drug development [1]. Emulate, a biotech company, modified these microfluidic biosensors to create “organ-on-a-chip” sensors that enable the study of drug-body interactions without invasive procedure [2]. A similar miniaturization occurred with microcantilever to nanocantilever biodiagnostic systems. Cantilever sensors are micro-scale platforms that physically or chemically react to external bending forces of the cantilever. The cantilever is suspended at one end and vibrates like a diving board. When the analyte re-binds onto the cantilever, the biosensor detects minute changes in weight or, even recently, electrical signal activation [3].
Quantum dots (QDs) are semiconductor nanoparticles that possess unique optical and electronic properties. Often built from ionic compounds in a core-shell structure, QDs owe their distinct characteristics to their extremely small size, which subject them to the laws of quantum mechanics. The center of a QD is covered by a shell of compatible material with differing semiconductivity. Scientists have also synthesized metal-free QDs using silicon and germanium. When implemented into nanomedical sensors, QDs are coated with a stable polymer shell to prevent cadmium poisoning. The stabilizing coat also ensures that UV irradiation does not invoke the material to seep into the bloodstream or other tissue. This is essential to avoid introducing potential toxins into tissues or circulation as QDs are used inside the body – examples such as these demonstrate that nanotechnology is quickly becoming readily implementable in biomedical settings.
QDs have proven advantageous for high-contrast fluorescent imaging in comparison to traditional organic dyes. First, their brightness levels are stronger than usual markers. To quantitatively compare the two brightness levels, scientists examine a value called the extinction coefficient, which measures a substance’s ability to reflect light. QD’s have higher extinction coefficients, and higher resultant brightnesses, compared to fluorescent dyes. Second, QDs can withstand more light exposure in comparison to typical organic dyes or fluorescent proteins. In cancer research projects that require longer-term targeted imaging, stem cell probes are conjugated with QDs to retain both fluorescence and immunogenicity. However, they may also have limitations in their role in nanomedicine. UV light overexposure may photolytically dissolve the protective shell over time, which heightens the risk of toxic blood poisoning or tissue damage.
Nanoparticles may also be used in pharmacokinetic drug delivery. Due to their small size, nanoparticles are easily endocytosed by cells without any major disruption to the membrane bilayer. Suspending small doses of drugs within these particles, especially drugs with poor solubility in water, enables highly efficient drug delivery throughout the body and ensures action at the targeted location [4]. Nanoparticles may also be tagged with proteins, allowing for the diagnosis and treatment of some diseases. However, nanoparticles are difficult to degrade and often remain in blood circulation for prolonged periods to enable a steady pharmacokinetic release. Researchers in nanomedicine have raised concerns about nanoparticles being made of materials that may cause harm to the body during prolonged exposure. To avoid potential poisoning or toxicity reactions, researchers have been examining “green” materials that are compatible with most physiological tissues to fabricate pharmacokinetic nanoparticles.
Nanoscale piezoelectric crystals have also demonstrated remarkable efficiency when converting mechanical to electrical energy. Piezoelectric materials acquire electric charge in response to external forces, and have garnered a reputation of ensuring high sensitivity and reliability [5]. Further technological advancements in nanoscale materials have led to the conception of miniature piezoelectric generators. These generators could prove useful as a longer-lasting alternative to batteries in biomedical devices. This would be particularly useful in surgically implanted devices, where battery replacement would involve invasive surgery. Each surgical procedure subjects the patient to an increased risk of complications, and multiple surgeries may place greater financial compensation on the patient’s family. Reducing the number of procedures required for maintenance on a patient’s medical devices will help to minimize undue burdens on patients.
While the nanomedical research community is still cautious about using QDs in vivo, scientists are becoming more comfortable with conducting in vitro research projects with this technology, especially in observing single-cell migration in embryonic development and metastatic malignant cancer. Nanomedical researchers have expressed interest in studying the antibacterial properties of QDs. In Singapore, a research team discovered that nanoparticles show promise in killing bacteria on a dose-dependent basis [6]. A separate research team in Iran also published research demonstrating the effectiveness of QDs and similar nanoparticles in combating both gram-positive and gram-negative bacteria [7]. Zinc oxide QDs are strongly photoluminescent, and oxygenating the surface of these QDs enables the capture of bacteria as well as the major functional groups of plasma membrane proteins. The use of QDs in identifying localized infections while simultaneously battling them could prove extremely useful in further antibacterial studies as well as an antibiotic line of defense.
Scientists and researchers are still working to discover the full utility that nanomedical technology may have to offer in the future. Nanofluidic and nanocantilever systems, QDs, and piezoelectric crystals exceed experimental measures of success in trials, but it is difficult to determine the true efficacy of these nanomaterials due to insufficient observed cases of live implementation in clinical patient-care settings. As research advances in this field, we may approach an era of more renewable, sustainable, and biocompatible materials, where much of our medical standard-of-care devices, from the heavy-duty to microscale, will take advantage of nanotechnology.
[1] Bhagat, Stuti. et al. 2022. “Chapter Seven – Cultivating Human Tissues and Organs Over Lab-on-a-chip Models: Recent Progress and Applications”. Progress In Molecular Biology and Translational Science, no. 187: 205-240. https://doi.org/10.1016/bs.pmbts.2021.07.023
[2] Emulate Bio. “Human-Relevant Models for Complex Biology.” Accessed November 16, 2022. https://emulatebio.com/organ-chips/
[3] SoltanRezaee, Masoud. et al. 2020. “Simulation of an Electrically Actuated Cantilever as a Novel Biosensor.” Scientific Reports, no. 10: article 3385. https://doi.org/10.1038/s41598-020-60296-9
[4] Patra, Jayanka. et al. 2018. “Nano Based Drug Delivery Systems: Recent Developments and Future Prospects.” Journal of Nanobiotechnology, vol. 16, no. 71 (September). https://doi.org/10.1186/s12951-018-0392-8
[5] Pohanka, Miroslav. 2018. “Overview of Piezoelectric Biosensors, Immunosensors and DNA Sensors and Their Applications.” Materials (Basel), vol. 11, no. 3: 448 (March). https://doi.org/10.3390/ma11030448
[6] Lu, Zhisong. et al. 2008. “Mechanism of Antimicrobial Activity of CdTe Quantum Dots.” Langmuir, vol. 24, no. 10, 5445-5452. https://pubs.acs.org/doi/10.1021/la704075r
[7] Abdolmohammadi, Mohammed H. 2016. “Application of New ZnO Nanoformulation and Ag/Fe/ZnO Nanocomposites as Water-Based Nanofluids to Consider In Vitro Cytotoxic Effects Against MCF-7 Breast Cancer Cells.” Artificial Cells, Nanomedicine, and Biotechnology, vol. 45. no. 8: 1769-1777. https://doi.org/10.1080/21691401.2017.1290643