Module 2 reviews selected biomedical nanotechnology applications that have been shown to have tremendous promise for mankind:
- Drug Delivery
- Imaging and Diagnostics
- Cancer Detection
- Tissue Regeneration
Biotechnology and molecular biology advances over recent years have resulted in a large number of novel molecules with the potential to revolutionize the treatment and prevention of disease. However, such potential is severely compromised by significant obstacles to delivery of these drugs in vivo. These obstacles are often so great that effective drug delivery and targeting is now recognized as the key to effective development of many therapeutics. Advanced drug delivery and targeting can offer significant advantages to conventional drugs, such as increased efficiency, convenience, and the potential for line extensions and market expansion.
The emergence of nanotechnology is likely to have a significant impact on drug delivery sector, affecting just about every route of administration from oral to injectable. In addition to deliverance of the therapeutic agent, there are other benefits including the potential for lower drug toxicity, reduced cost of treatments, and improved bioavailability.
Nanotechnology is also opening up new opportunities in implantable delivery systems, which are often preferable to the use of injectable drugs, because the latter frequently display first-order kinetics (the blood concentration goes up rapidly, but drops exponentially over time). This rapid rise may cause difficulties with toxicity, and drug efficacy can diminish as the drug concentration falls below the targeted range. Implantable time release systems may help minimize peak plasma levels and reduce the risk of adverse reactions, allow for more predictable and extended duration of action, reduce the frequency of re-dosing and improve patient acceptance and compliance.
Emerging nano-drug delivery vehicles include dendrimers, micelles, emulsions, nanoparticles, and liposomes. The picture below illustrates the nano-size dimensions for these technologies. We will review these technologies in detail in the upcoming modules.
Imaging and Diagnostics
Medical imaging refers to the techniques and processes used to create images of the human body (or parts thereof) for clinical purposes (medical procedures seeking to reveal, diagnose or examine disease) or medical science (including the study of normal anatomy and physiology).
Conventional methods include:
- Electron microscopy
- Magnetic resonance imaging (MRI)
- Nuclear medicine
- Photoacoustic imaging
- Breast Thermography
Nanotechnology offers the promise of delivering in vivo Imaging. Biomimetic nanoconstructs can be used to deliver imaging agents to malignant tissues and suspected areas within the body. Nanoconstructs under investigation include the following:
- Quantum dots
- Nanopore technology
- Gold/silver nanoparticles
- Cantiliver arrays
- Nanoparticle based immunoassays
- Protein nanoarrays
- Nanoparticle probes
- DNA nanomachines
The nanoparticles are unique in that they can be engineered to survival in the biological system through their size, wettability, bioconjugation (attachment to bioentities such as proteins), and biorecognition. Conventional contrast agents fall victim to rapid photobleaching (cannot retain color after extended periods of time in vivo), broad (non specific) emission spectrum, lack of specificity to target cells, and influenced by different biological environments (pH, temperature).
Cancer is defined as any malignant growth or tumor caused by abnormal and uncontrolled cell division. Cancer cells may also spread to other parts of the body through the lymphatic system or the blood stream.
Cancer is one of the leading causes of death across the globe. Studies show that early detection of the disease due to routine screening and good better understanding of the pathophysiology of tumor progression has created new treatment opportunities.
Solid tumors are surgically removed, with the remaining cancer cells are managed through treatment options such as chemotherapy, radiotherapy, and immunotherapy. However, once the cancer becomes chronic, then the treatment options are limited. Then, chemotherapy remains the choice of treatment. Challenges associated with chemotherapy include the poor accessibility of antineoplastic agents to the tumor. This requires higher doses, and the nonselective nature of these agents causes severe toxicity in the body.
What is tissue? Tissues are mainly composed of cells and the secreted extracellular matrix. These structures organize into functional subunits. Living organisms regenerate a lost or damaged part if the part regrows so that the original function is restored.
Tissue engineering is defined as the application of biological, chemical, and engineering principles toward the repair, restoration, or regeneration of living tissues using biomaterials, cells, and factors alone or in combination. This platform stems from the demands by surgeons in regenerating functionally active tissue to replace those lost due to trauma, congenital malformations or various disease processes.
The goal of tissue engineering is to replace the currently used grafts/prostheses with complex constructs that support the regeneration of lost or damaged tissue.
Scaffolds are one of the major products of tissue engineering. The material used to produce the scaffold must be biocompatible and biodegradable. Here, the material must gradually degrade into natural biocompatible products that don’t exhibit an inflammatory response in the body long term. Scaffold materials under investigation include synthetic (PLA, PLGA, urethane) and natural polymers (collagen, chitosan).
There are several design issues that must be considered when selecting a material to be used as a scaffold for bone tissue engineering. On a high level, the cell delivery system material must exhibit morphological similarities to the extra cellular matrix. Specifically, this includes the follow criteria for material selection:
- Capable of supporting cell growth
- Good mechanical properties
Biopolymers, ceramics, and composites have been investigated for this application.
Modulating cellular function to enhance tissue regeneration is also important for this application. The material must have the ability to incorporate cells. This can involve the conjugation of peptides or other proteins to the surface that provide a linkage between the scaffold material and the cells. The scaffold material must have the ability to incorporate growth factors.
To further mimic the surface characteristics of the extra cellular matrix, the scaffold material must possess nanoscale features. This could be in the form of nanofibers or nanopartices. Nanofibers have the advantage of ultra fine, continuous fibers that yield strength and a high level of porosity. Nanoparticles (fillers), on the other hand, can be included can be included in the polymer matrix. For example, nano size titania particles can be incorporated into biodegradable polymers such as PLGA. This has been shown to promote osteoblast growth relative to conventional materials.
The illustrations below shows several micro-fabricated scaffolds.
The scaffold material must also meet certain mechanical properties as part of the design requirements. The material must mimic of the unique mechanical properties of native bone tissue. Here, the material used to produce the scaffold must provide mechanical support during tissue growth.
Finally, it would be advantageous for the scaffold material to be injectable as a liquid paste into the cavity area. The paste would active (or harden) using ultraviolet light, for example.
This supplemental reading below reviews the significance and recent advances of gene/drug delivery to cancer cells, and the molecular imaging and diagnosis of cancer by targeted functional nanoparticles.
This supplemental reading below reviews the possibilities and challenges for targeted drug delivery in cancer therapy.
This article reviews current strategies using nanobiomaterials to improve current orthopedic materials and examines their applications in bone tissue engineering.
This article reviews nanotechnology and tissue engineering and scaffolds.