Role of Nanobiotechnology in Drug Discovery

Nanotechnologies - nanoparticles and various nanodevices such as nanobiosensors and nanobiochips - have the potential to improve drug discovery. Microfluidics has already proven useful for drug discovery and, through further miniaturisation, nanotechnology will improve the ability to fabricate massive arrays in small spaces using nanofluidics.
Nanoparticles such as gold nanoparticles and quantum dots have attracted considerable attention recently with their unique properties for potential use in drug discovery.
1. Nanobiotechnology for Target Validation
Multivalent attachment of small molecules to nanoparticles can increase specific binding affinity and reveal new biological properties of such nanomaterial. Multivalent drug design has yielded antiviral and antiinflammatory agents several orders of magnitude more potent than monovalent agents. Parallel synthesis of a library has been described, which is comprised of nanoparticles decorated with different synthetic small molecules. Screening of this library against different cell lines led to the discovery of a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. This multivalent approach could facilitate the development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types. It has potential applications in high-throughput drug discovery, target validation, diagnostics and human therapeutics.
2. Nanotechnology-based Drug Design at Cell Level
To create drugs capable of targeting human diseases, one must first decode exactly how a cell or a group of cells communicates with other cells and reacts to a broad spectrum of complex biomolecules surrounding it. But even the most sophisticated tools currently used for studying cell communications suffer from significant deficiencies and typically can only detect a narrowly selected group of small molecules or, for a more sophisticated analysis, the cells must be destroyed for sample preparation. A nanoscale probe, the scanning mass spectrometry (SMS) probe, can capture both the biochemical makeup and topography of complex biological objects. The SMS probe can help map all those complex and intricate cellular communication pathways by probing cell activities in the natural cellular environment, which might lead to better disease diagnosis and drug design on the cellular level.
3. Nanomaterials as Drug Candidates
In addition to the use of nanobiotechnology for drug discovery, some drugs are being developed from nanomaterials. Well-known examples of these are dendrimers, fullerenes and nanobodies. Specialised chemistry techniques allow precise control over the physical and chemical properties of the dendrimers. Polyvalent dendrimers interact simultaneously with multiple drug targets. They can be developed into novel targeted cancer therapeutics. Polymer–protein and polymer–drug conjugates can be developed as anticancer drugs. Dendrimer conjugation with low molecular weight drugs has been of increasing interest recently for improving pharmacokinetics, targeting drugs to specific sites and facilitating cellular uptake. Opportunities for increasing the performance of relatively large therapeutic proteins such as streptokinase (SK) using dendrimers have been explored in one study. Using the active ester
method, a series of streptokinase–polyamidoamine (PAMAM) G3.5 conjugates were synthesised with varying amounts of dendrimerto- protein molar ratios. All of the SK conjugates displayed significantly improved stability in phosphate buffer solution, compared with free SK. The high coupling reaction efficiencies and the resulting high enzymatic activity retention achieved in this study could lead to a desirable approach for modifying many bioactive macromolecules with dendrimers.
A key attribute of the fullerene molecules such as C60 is their numerous points of attachment, allowing for precise grafting of active chemical groups in 3D orientations. This attribute, the hallmark of rational drug design, allows for positional control in matching fullerene compounds to biological targets. In concert with other attributes, namely the size of the fullerene molecules, their redox potential and its relative inertness in biological systems, it is possible to tailor requisite pharmacokinetic characteristics to fullerene-based compounds and optimise their therapeutic effect. A number of water-soluble C60 derivatives have been suggested for various medical applications. These applications include neuroprotective agents, HIV-1 protease inhibitors,bone-disorder drugs, transfection vectors, X-ray contrast agents, photodynamic therapy agents and a C60–paclitaxel chemotherapeutic. Nanobodies, derived from naturally occurring single-chain antibodies, are the smallest fragments of naturally occurring heavy-chain antibodies that have evolved to be fully functional in the absence of a light chain. Like conventional antibodies, nanobodies show high target specificity and low inherent toxicity; however, like small-molecule drugs, they can inhibit enzymes and can access receptor clefts. Nanobodies can address therapeutic targets not easily recognised by conventional antibodies such as active sites of enzymes.