Since their discovery in 1961, liposomes - nanoscale vesicles composed of phospholipids - have been developed as nano-vectors that are used for a variety of biomedical applications including diagnostic imaging, gene therapy, biosensing and targeted drug delivery. In fact, the FDA-approved drugs Ambisome, Doxil and DaunoXome all contain liposomal formulations. Such liposomes are typically comprised of glycerol-based phospholipids that contain a hydrophilic (water-soluble) head-group and one or two hydrophobic (water-insoluble) hydrocarbon chains of varying length. In aqueous solution, these phospholipids self-assemble into a lipid bilayer, with the hydrophilic lipid groups oriented toward the aqueous solution and the hydrophobic groups protected in the bilayer's interior. The bilayers form spherical vesicles that are used to carry drugs and diagnostic imaging agents to sites of interest within the body. The hollow interior of the vesicles is hydrophilic and can easily encapsulate a variety of hydrophilic drugs or imaging agent molecules, which are then released from the liposomes in a controlled fashion. But what about hydrophobic molecules - those that aren't water-soluble and therefore aren't easily encapsulated within the interior of traditional phospholipid liposomes? Many beneficial, yet water-insoluble drugs do exist, but the current methods used to administer to these drugs to patients, such as dissolving them in alcohols, castor oil or other hydrophobic liquids for injection, can cause patients much discomfort or other side effects. For these reasons, the development of a nano-vector with a hydrophobic interior - one that could successfully encapsulate and release hydrophobic molecules - is of great interest to the nanomedicine community.
The process of bringing a major new drug to market, from discovery to marketing, takes about 10-12 years and costs an average of $500-$800 million in industrialized countries. And still, most drugs fail before they even make it to market. About 80 percent of drugs never make it through their clinical trials. Of the medications that actually enter consumer use, an average of just 60 percent provide therapeutic benefits to patients. For a pharmaceutical company the results of the process designing new drugs leads to a library of novel compounds that are created with a specific goal, a given set of criteria. Often these criteria include the selectivity for a particular known receptor. A new drug treatment can be discovered by testing those drugs on other receptors by trial and error. Since this is a very expensive approach, pharma companies have developed sophisticated computer models that help reduce the risk and uncertainty inherent in the drug-development process. Here, one starts with a computer model of the structure of a receptor and a drug. The goal is to predict by simulation how a drug will dock (interact with a receptor), or how the receptor will fold. Drug design based on mathematical models will also become a massive task within the emerging field of nanomedicine. Although nanotechnology offers great visions of improved, personalized treatment of disease, at the same time it renders the problem of selecting the candidates for biological testing astronomically more complex. The new notion of 'design maps' for nanovectors - similar to the concept of the periodic table for chemical elements - could provide guidance for the development of optimized injectable nanocarriers through mathematical modeling.
Carbon nanotubes (CNTs) have shown promise as an important new class of multifunctional building blocks and innovative tools in a large variety of nanotechnology applications, ranging from nanocomposite materials through nanoelectronics to biomedical applications. The exploration of CNTs in biomedical applications is well underway and exploratory uses have included CNT-coated implants, drug delivery and CNTs as components of biosensors. Notwithstanding the still not satisfactorily addressed issue of toxicity, CNTs' properties such as high strength, high electrical and thermal conductivities, and high specific surface area render them particularly useful in the fabrication of nanocomposite-derived biomedical devices. In one particular area - biomaterials applied to bone - CNTs are anticipated to improve the overall mechanical properties for applications such as high-strength arthroplasty prostheses expected to remain in the body for a long time, or fixation plates and screws that will not fail or impede healing of bone. In addition, CNTs are expected to be of use as local drug delivery systems or scaffolds to promote and guide bone tissue regeneration. A new study by Japanese scientists clearly demonstrates that multi-walled CNTs (MWCNTs) have good bone-tissue compatibility, permitting bone repair and becoming closely integrated with bone tissue. Furthermore, under certain circumstances, their results indicate that MWCNTs accelerate bone formation.
Much has been written about the fascinating properties of spider silk, a biopolymer that is stronger than steel and more elastic than rubber. The silken threads possess a unique combination of mechanical properties: strength, extensibility and toughness. Of course this begs the obvious question: How is it possible that spider silk, produced by little creatures that evolved about 400 million years ago, can be as strong as steel - a modern alloy that plays a critical role in our infrastructure and which still attracts considerable R&D investments in its production technology? What is perplexing is that the atomic interactions (H-bonds) in spider silk are actually 100 to 1,000 times weaker than those in steel, or than those in the superfiber Kevlar, where covalent bonds are used. Hydrogen bonds are the basic chemical bonds that hold together proteins, similar to trusses and beams in buildings, and play a key role in controlling the behavior of these structures. In order to reach silk's mechanical properties, most synthetic materials must be much denser, thus much heavier and consume much more energy during their synthesis and transport. New analysis performed at MIT's Laboratory for Atomistic and Molecular Mechanics shows that the intriguing strength of spider silk may be made possible by precisely controlling the number and the geometry of H-bonds at a characteristic length scale. The physical concept is that by making many small elements work together cooperatively, the weaknesses of the individual components can be overcome. All this must happen at the nanoscale in order to be effective.
Photodynamic therapy (PDT) is a cancer treatment that combines a chemical compound, called a photosensitizer, with a particular type of light to kill cancer cells. The treatment works like this: the photosensitizing agent is injected into the bloodstream. The agent is absorbed by cells all over the body, but stays in cancer cells longer than it does in normal cells. One to three days after injection, when most of the agent has left normal cells but remains in cancer cells, the tumor is exposed to light. The photosensitizer in the tumor absorbs the light and produces an active form of oxygen (singlet oxygen) that destroys nearby cancer cells. PDT has been used for the past 30 years and is a treatment that works. PDT takes very little time, is often done as an outpatient, can be accurately targeted to the affected area, can be repeated, and has no long-term side effects. It also isn't as expensive or invasive as some other cancer treatment options. The limitation of this form of cancer treatment is that the light needed to activate most photosensitizers cannot pass through more than one centimeter of tissue. For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities. PDT is also less effective in treating large or deep tumors, because the light cannot pass far into these tumors. Researchers have now proposed a new PDT system in which the light is generated by x-ray scintillation nanoparticles with attached photosensitizers. When the nanoparticle-photosensitizer conjugates are targeted to tumors and stimulated by x-rays during radiotherapy, the particles generate visible light that can activate the photosensitizers for photodynamic therapy. Therefore, the radiation and photodynamic therapies are combined and occur simultaneously, and the tumor destruction can be more efficient. More importantly, it can be used for deep tumor treatment as x-rays can penetrate through tissue.
Walk into an intensive care unit and you're likely to see many of the patients sporting a 'central line' - a plastic tube placed in a large vein that goes to the heart. A central line is a very efficient way to pump nutrients, antibiotics or other drugs directly into the bloodstream. Unfortunately it is also a cause for bloodstream infections (sepsis) and central lines remain an important cause for hospital deaths. An estimated 200,000 bloodstream infections occur each year in the U.S. alone, the majority associated with the presence of an intravascular catheter. The Institute for Healthcare Improvement (IHI) estimates the yearly death toll from blood infections related to intravenous lines to be as high as 28,000. Numerous pathogens can cause sepsis and the death toll could be reduced if the specific pathogen could be identified more quickly than it is usually done today using blood cultures (the laboratory examination of a blood sample to detect the presence of disease-causing microorganisms). One solution would be to determine the pathogen's DNA, requiring a rapid DNA assay with the potential for mutant identification and multiplexing. Current DNA assays are based on thermal dehybridization or melting of the DNA duplex helix - the melting temperature of DNA is determined by its base sequence - a process that can take up to an hour. Researchers in Germany have developed a novel technique that allows for DNA analysis in the millisecond range. Their method has great potential to vastly improve the speed of pathogen detection.
Hollow polymeric micro- and nanoparticles have numerous existing and many anticipated applications in drug delivery, ranging from the controlled release of drugs, cosmetics, inks, pigments or chemical reagents to the protection of biologically active species, and removal of pollutants. Encapsulation also allows drug targeting via cell and tissue-specific ligands. There is a variety of methods available for synthesis of polymer microspheres with hollow interiors. The hollow particles are most commonly prepared by coating the surfaces of colloidal templates with thin layers of the desired material (or its precursor), followed by selective removal of the templates by means of calcination or chemical etching. For polymers, methods such as emulsion polymerization, phase separation, cross-linking of micelles and self-assembly have also been demonstrated for generating hollow structures. The hollow polymer particles produced by these methods present either a closed-core-shell structure or many small pores on their surface. However, these synthetic approaches present limitations on the choice of polymers that can be produced as hollow microspheres. Also, the number, size and shape of the surface pores can not be easily manipulated. When these materials are used for encapsulation-related applications, the encapsulation of the desired functional materials is usually too slow and/or too labor-intense. These problems have motivated scientists to develop the synthesis of a new class of polymer microspheres, which they called microscale fish bowls. Their unique feature consists in the presence of one big pore on their surface that allows easy and fast diffusion of a functional material to be encapsulated. Another new feature is that this newly developed method presents no limitations on the choice of polymers that can be produced as microscale fish bowls.
Nature has excelled in designing molecular motors, something nanotechnology researchers are still having a hard time with. The potential for nano-actuators (a nanoscale device that creates automatic motion by converting various forms of energy to rotary or linear mechanical energy) is huge - basically any active system that performs some kind of work requires an energy source. Applications reach from simple pumps on lab-on-a-chip devices to move nanoliters of fluid around to nanoscale motors for nanorobotic systems. One of the challenges of designing such a motor for the nano realm is that during the design of a nano-actuator the tradeoffs among range of motion, force, speed (actuation frequency), power consumption, control accuracy, system reliability, robustness, load capacity, etc. must be taken into consideration. Most microscale systems are currently achieved by relatively large external actuators such as syringe pumps, or high voltage power supplies, which negates the advantages of the microfabricated systems. That's why scientists are quite intrigued by the opportunity to use biological organisms to construct mechanical actuators in engineered systems at the micro- or even nanoscale. An extremely powerful biological motor is the bacterial flagellar motor found in organisms such as Escherichia coli or Serratia marcescens. Bacteria draw chemical energy directly from their environment and are able to survive in a wide range of temperature and pH. What makes bacterial propulsion system interesting for nanotechnology researchers is that bacteria are exquisitely sensitive to a wide variety of external stimuli. So far, scientists have managed to control them en masse through light (phototaxis) and chemical (chemotaxis) sensory mechanisms. In a recent example of successful use of live bacteria as mechanical actuators, scientists have built a microfluidic pump powered by self-organizing bacteria.