Bionanotechnology: Advances and Future Perspectives

Dr. Mohammad Abul Farah, Seoul, South Korea

Bionanotechnology is an exciting multidisciplinary field that has enormous potential to develop new science and applications such as novel materials, devices, biosensors, drug delivery, etc. It is a rapidly growing integrative field that encompasses contributions from various disciplines, ranging from engineering and computational sciences to physics, chemistry and biology. Bionanotechnology is a subsidiary branch of nanotechnology, which is often described by the terms such as biomedical nanotechnology, nanobiotechnology, biomolecular nanotechnology and nanomedicine. Nanotec hnology research may be defined as the creation, design, and manipulation of structures or particles with dimensions smaller than 500 nanometers (nm). Within this size range, the structures or particles have properties that can be tuned by changing the material’s dimensions.
It is expected that nanotechnology will be developed at several levels: materials, devices and systems. Considering scientific knowledge and commercial applications, the nanomaterials level is the most advanced at present. However, in the last few years, new avenues and promises have been created for nanotechnology research because the biological and medical research communities have exploited the unique properties of nanomaterials for various applications for example contrast agents for cell and animal imaging and therapeutics for treating cancer. Some of the applications of nanomaterials to biology and medicine include drug and gene delivery, fluorescent biologi cal labels, detection of proteins, bio-detection of pathogens, probing of DNA structure, tissue engineering, tumor destruction via hyperthermia, separation and purification of biological molecules and cells. The integration of nanomaterials with biology has led to the development of di agnostic devices, contrast agents, analytical tools, therapy, and drug delivery vehicles. Over the last 2 decades, a variety of nanoscale vehicles, including gelatin, ceramic, liposomes, and micelles, have been under development for therapeutic use. Recent improvements in engineering at the nanoscale level have lead to the development of a variety of new, novel nanoscale platforms such as quantum dots, nanoshells, gold nanoparticl 6 Manthan magnitude more resistant to photobleaching than their organic fluorophore counterparts. When QDs are used in biological research and applications, these optical properties will lead to improved detection sensitivity for analysis and to simplification in experimental and instrumental design. Because QDs have fluorescence properties, they have been rapidly adapted into many biological and medical research laboratories. For in vitro applications, QDs conjugated to antibodies and peptides are used for labeling receptors on fixed and live cells and tissues; QDs conjugated to oligonucleotides are used for genetic detection. For in vivo applications, QDs as contrast agents for cancer imaging has been successfully demonstrated.
Nanoshells Nanoshells (approximately 10–300 nm in dimension) are composed of a dielectric core, usually silica, surrounded by a thin metal shell, typically gold. The optical properties of nanoshells are different from quantum dots. Nanoshells rely on the plasmonmediated conversion of electrical energy into light. Similar to quantum dots, nanoshells have the ability to be tunable optically and have mission/absorption properties that range from the UV to the infrared. Nanoshells are attractive because they offer in vitro and in vivo imaging and potential therapeutic properties similar to those of quantum dots without the potential for heavy metal toxicity. A potential limitation of nanoshells is their relatively large size compared with quantum dots. The ability of specifically engineered nanoshells to act as photoabsorbers with resultant heat generation has powerful potential therapeutic implications for the use of nanoshells in photothermal ablation. Gold Nanoparticles Gold nanoparticles are attractive because gold has been approved and used for treatment of human disease and they are relatively easy to synthesize. Gold nanostructures are used as contrast agents in electron microscopy or in vitro experimentation based on their ability to scatter visible light. Gold nanoparticles also have been used as a platform for novel experimental cancer therapy. It was demonstrat ed that systemically delivered gold nanoparticles (size, approximately 33 nm) conjugated to tumor necrosis factor (TNF) accumulated in tumors. Gold particles also have been used to enhance sensitivity to external beam radiation.58 Systemically administered gold nanoparticles (size, 1.9 nm) accumulated in a murine subcutaneous tumor model and greatly

photothermal ablation applications in vitro.83 SWNTs coupled to paramagnetic gadolinium particles are being developed for use as a high- performance MRI contrast agent.

Future perspective

Bionanotechnology offers an extraordinary, paradigm-changing opportunity to make significant advances in diagnosis and treatment of various diseases. Nanotechnology is also expected to accelerate fundamental biomedical research via the creation of novel state-of-the-art tools. This emerging field is exciting because of its possibilities. Areas of greatest clinical impact likely include novel, targeted drug-delivery vehicles, molecularly targeted contrast agents for cancer imaging, targeted thermal tumor ablation, and magnetic field targeting of tumors. Bionanotechnology also is progressing rapidly with regard to in vivo imaging and therapeutics. This progress very likely will have important implications for management of the cancer patient. Future advances in nanotechnology research and development likely will be associated with the further development of novel, high-impact approaches to cancer diagnosis and treatment. As it stands now, it could be predicted that one day, researchers will incor porate multifunctionality into nanomaterials. With these multifunctional


paramagnetic nanoparticles, carbon nanotubes, which currently are under development and investigation. These nanotools have been mainly used for imaging, drug delivery, photothermal ablation, drug targeting etc. Below are the few examples of current bionanotechnology research and progress.

Lipid-based vehicles Liposomes, micelles, and polymersomes are nanoscale lipid-based vehicles. These lipid-based vehicles have been used primarily for increasing the solubility of hydr ophobic chemotherapeutics and for limiting drug toxicity. Novel preparations of these compounds recently have been developed with the objective of overcoming some of those limitations. Liposomes coated with poly(ethylene) glycol (PEG), so-called stealth liposomes, have increased bioavailability si gnificantly because of reduced, nonspecific reticuloendothelial system (RES) uptake. Liposomes constructed with novel lipid polymers have resulted in significantly increased membrane stability and bioavailability. Micelles and liposomes coated with tumor-specific antibodies have been used for tumor targeting. Liposomes that recently were synthesized with self hydrolysable lipids may allow for time- controlled release of drugs.
Quantum Dots (QDs) QDs are defined as particles with physical dimensions smaller than the exciton Bohr radius; this gives rise to a unique phenomenon known as quantum confinement. Quantum confinement, which refers to the spatial confinement of charge carriers (ie, electrons and holes) within a material, embarks QDs with unique optical and electronic properties that are unavailable to semiconductors in bulk solids. Quantum dots are novel semiconductor nanocrystals composed of an inorganic elemental core (e.g., cadmium, mercury) with a surrounding metal shell and have an intrinsic fluorescence emission spectra wavelength between 400 nm and 2000 nm, depending on their size and composition. Quantum dots possess unique optical properties that not only allow them to be tunable to discreet narrow frequencies but also are an order of enhanced local X-ray therapy. Gold nanocages, a new type of gold nanoparticle, may be constructed to generate heat in response to NIR light and, thus, also may have a potential application in photothermal ablation. Gold nanoparticles are widely used in immunohistochemistry to identify protein-protein interaction.

Paramagnetic Nanoparticles
Functionalised magnetic nanoparticles have found many applications including cell separation and probing. Super paramagnetic iron oxide contrast agents consisting of 50-nm to 100-nm particles were developed and are attractive because they have much greater magnetic susceptibility than traditional magnetic resonance (MR) contrast agents, such as gadolinium. Ultra small, super paramagnetic iron oxide nanoparticles have been used clinically in humans to characterize lymph node status in patients with breast cancer, lung cancer, prostate cancer, endometrial cancer, and cervical cancer. It has been shown experimentally that gadolinium- containing nanoparticles coated with folate or PEG accumulates in tumors. Nanosized contrast agents are under development to improve the utility of MRI and computed tomography (CT) in imaging cancer. The ability to monitor apoptosis in vivo may represent a method for monitoring response to cancer therapy. Ligands that are specific for apoptosis (e.g., the C2 domain of synaptotagmin and annexin V) have been conjugated to iron oxide nanoparticles and, experimentally, have demonstrated an ability to bind apoptotic cells in vitro and in vivo.

Carbon Nanotubes Carbon nanotubes are carbon cylinders composed of benzene rings, their use in biological applications is evolving. Carbon nanotubes have been used as gene therapy delivery vectors. Nanotubes can be made in different sizes and, at small sizes, have been shown to be internalized intracellularly through endocytosis. Recently, investigators have functionalized nanotubes for biologic applications by adsorbing different molecules and antigens to their surface so that they specifically may target tumor cells. Folic acid (FA) and fluorescent tag- conjugated, singlewalled carbon nanotubes (SWNTs), a type of nanotube has been created specifically to target HeLa cells, in vitro. These cells actively endocytosed these SWNTs and were identified through the fluorescent tag under c onfocal microscopy. Furthermore, SWNTs were engineered to absorb NIR light and subsequently were used fo nanodevices, molecules and motors will guide nanomaterial movements, sensors for diagnosis, actuators (which are connected to the sensor) to release therapy, and a secondary sensor to monitor the disease as it is being treated. The foundation of nanotechnology is quickly being put into place, and some applications of nanotechnology in biology have surfaced, although these applications are nowhere near the complexity of the described multifunctional device. In conclusion, bionanotechnology is still in their infancy, but one day it would be capable of tracking life within the cells in real time, and of course without destroying them.

About the Author: Mohammad Abul Farah attended Aligarh Muslim University in India where he received his M.Sc. and Ph.D. in Zoology with specialization in Genetics. He also served as Senior Research Fellow of Council of Scientific and Industrial Research, India. At present, he is working as a Research Scientist in Proteonik Inc., a biotechnology venture company based in Seoul, South Korea, on Diabetes research focusing on insulin signaling pathway.




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