Nanotechnology and its applications in surgery

It has been suggested that medicine will change more in the next 20 years than it has in the past 2000. This may be true, as a result of advances in biotechnology and the recent emergence of nanotechnology. The concept of nanotechnology was first introduced by the quantum theorist and Nobel laureate Richard Feynman. Nanotechnology deals with the manipulation and control of nanomaterials with at least one dimension below 100 nm. Nanosized particles have been incorporated successfully into modern surgical practice, offering novel minimally invasive imaging techniques, improved drug delivery systems and providing a basis for the development of engineered organs. This article highlights some of the latest advances. Beyond these current applications lies the promise of incorporating nanosized robotics into medical and surgical practice. Nanorobotics is the manufacture of ‘smart’ nanodevices that can subsequently be exploited for diagnostic and therapeutic purposes1. Although minimally invasive image-guided endovascular interventions are well established in cardiovascular surgery, catheterization is limited by vessel diameter. Vessels with a small diameter in the range 4–5 µm, such as those in capillary beds, lie beyond current technologies but may be entered by nanorobots2. Nanoparticles have a high surface area to volume ratio that confers mechanical, magnetic, optical and chemical properties superior to those of the original materials. They can be considered in three categories. Fullerenes are carbon allotropes that can adopt different shapes, such as carbon nanotubes. The cylindrical shape is derived from the hexagonal lattice of carbon atoms, forming a sheet that can be rolled up. This molecular arrangement confers considerable stiffness and tensile strength (50 times stronger than steel). Combined with an antithrombogenic surface, carbon nanotubes are suitable for applications such as vascular microcatheters and implants. Nanoparticles, for example quantum dots (QDs), can act as drug carriers or as labels for cell tracking. QDs are particularly suitable for imaging because they emit fluorescence at different wavelengths determined by particle size. Nanocomposites are multiphase solid materials where one of the phases has one, two or three dimensions of less than 100 nm. In tissue engineering, scaffolds are enhanced by nanoparticulate fillers which intercalate between layers or distribute evenly throughout to maximize surface area for component interaction. Fillers include silicones, carbon nanotubes, nanoclays and novel synthetic nanocomposites such as polyhedral oligomeric silsesquioxane (POSS). The latter confers superior physical properties such as mechanical strength and oxidative resistance to the composite. The amphiphilic nature of POSS increases the ability of the nanocomposite to support cell adherence and growth, making it ideal for tissue engineering. The main current applications of nanotechnology for surgeons are in the areas of development of surgical implants using nanomaterials, imaging, drug delivery and development of tissue engineering products, such as scaffolds with enhanced material–cell interaction. An example of this is the development of a scaffold for delivery of stem cells to replace defective retinal pigmented epithelial cells in age-related macular degeneration. Current imaging technologies for the diagnosis and staging of cancer have limitations. Fluorescent semiconductor nanocrystals (QDs) have narrow and size-tunable emission spectra spanning all the way from ultraviolet to near-infrared. Combined with prolonged photostability, high photoluminescence and high signal-to-noise ratio, QDs are particularly suitable for non-invasive imaging and can be used for identification and long-term in vivo monitoring of disease. QDs can be used in sentinel lymph node biopsy for staging breast cancer metastasis. Current detection methods based on lympho- scintigraphy and vital dyes can be confounded by background tissue autofluorescence. QDs emitting at the near-infrared region are associated with a decrease in tissue autofluor- escence and can be used in deep tissue imaging, making accurate and sensitive localization and subsequent excision of cancer foci possible3,4. QDs attached to paramagnetic ions can be used with magnetic resonance imaging (MRI). This combination exploits the high sensitivity of QD fluorescence and the high spatial resolution of MRI, acting synergistically to enhance the reliability of obtained data5. QDs can be conjugated to specific peptides to image specific tumour cells selectively in vivo. This concept may have a role in therapy. QDs preloaded with bioactive molecules (plasmid DNA, growth peptides) have been shown to prolong the viability of transplanted stem cells in experimental models6. Conjugation of pharmacological agents on to nanocarriers may be used for targeted drug delivery to improve efficacy and reduce systemic toxicity. Among nanoscaled drug delivery systems, liposomes and drug-conjugated nanoparticles for cancer treatment are of particular interest7. Liposomes are spherically arranged lipid bilayers that have the capacity to encapsulate drugs within their inner aqueous phase. Polyethylene glycol (PEG)-coated liposomes incorporating the anthracycline doxorubicin have a lower cardiotoxicity and greater efficacy than free drug. This formulation is currently in clinical trial for breast cancer. Experimentally, this conjugate was shown to be effective against doxorubicin-resistant colorectal cancer, raising the possibility that reformulation of existing drugs may be effective in drug-resistant cancers. Combinations of drugs and biocompatible polymers are also useful in reducing systemic toxicities. For example, PEGylated polymer-bound paclitaxel showed decreased toxicity without loss of chemotherapeutic potency in experimental models compared with the current formulation that utilizes organic solvents capable of eliciting hypersensitivity. Nanotechnology is highly applicable to the developing field of tissue engineering. Occlusive vascular disease may require intervention relying on stents or synthetic bypass grafts. Graft failure is often linked to endothelial dysfunction, leading to thrombus formation and subsequent complications. The ideal graft should resist intimal hyperplasia, have biomechanical properties resembling those of a healthy natural vessel and possess thrombo- resistant properties. The nanocomp- osite polymer POSS–poly(carbonate-urea)urethane (PCU) combines all three features. It also has an amphiphilic nature that repels platelets and confers antithrombogenic properties. The incorporation of a nitric oxide-releasing fumed silica nanoparticle into the polymer enhances antithrombogenicity. In situ graft endothelialization has been achieved in vitro using bioactive peptides associated with POSS-PCU. Endothelialization can be stimulated further by nanopatterning the graft luminal surface to promote cellular adhesion and function8. A different type of scaffold uses biomimetic nanofibres for endothelial regeneration. When aligned, nano- fibres result in great tensile strength and provide an axis for migration and aggregation of endothelial cells. Incorporating carbon nanotubes confers conductivity to the scaffold, allowing the application of external electric fields to manipulate cell behaviour. For bone replacement, limitations of current scaffolds include insufficient mechanical strength, limited cellular growth and minimal potential for osseointegration. Introducing nanoparticles to a polymer scaffold can reinforce its structure. For example, the incorporation of nanohydroxyapatite—a calcium phosphate ceramic found naturally in bone—into a biodegradable polyamide polymer resulted in an osteoconductive scaffold with comparable mechanical properties to natural bone. Carbon nanotubes, with their extraordinary mechanical strength, have also been used in nanocomposites for bone tissue engineering with a resulting threefold increase in bone tissue ingrowth, reduced inflammatory cell density and increased connective tissue organization in experimental models9. In order to exploit nanotechnology fully and minimize potential toxic effects, long-term health implications of nanoparticle use need to be investigated thoroughly. For example, nanoparticle size may mean that the blood–brain barrier can be crossed. Large surface area to volume ratios render nanoparticles biologically active. This may lead to inflammation and oxidative stress. Furthermore, for successful tissue engineering, scaffolds capable of providing the necessary oxygen and nutrients to densely packed cells in whole organs need to be developed. Advances in nanotechnological applications require a multidisciplinary approach using engineering, chemical and biomedical expertise. Only the surgeon can put these ideas into practice. The authors declare no conflict of interest.