NANOPARTICLES AS DRUG DELIVERY AGENTS

Molecular recognition is one of the central processes in drug action. The comparison and detection of binding sites are key steps in the prediction of potential interactions. Various biological macromolecules that interact with the drug molecule are enzymes, receptors, nucleic acids, membranes, carriers, proteins, etc. These are all targets for the drug action, and the structures of these targets are used to model and display the interactions with the drug structure. These interactions are crucial and must be understood before the design of a new molecule for better interactions. The intricate process of using the information contained in the thr ee-dimensional structure of a macromolecular target and related ligand-target complexes to design novel drugs is alternately called as structure-based drug design. Several approaches directed toward this task are available.

Chemotherapy is an important part of cancer treatment. In this, anticancer drugs are (Ozin and Yang, 2001) introduced into the circulatory system to transport anticancer drugs to the tumors. However, there are negative side effects of this treatment such as nonspecificity and toxicity of the drug. The drug can attack healthy cells and organs as well as the cancerous cells. Therefore, targeted drug delivery is being developed as one alternative to chemotherapy treatment to direct the drug to the specific area where the tumor is located, thereby increasing the amount of drug delivered at the tumor site and reducing the side effects. This is accomplished by the use of magnetic NPs to deliver the drug to its specific location. Generally, the magnetic NPs are coated with a biocompatible layer, such as gold or polymers, so that the anticancer drug can either be conjugated to the surface or encapsulated in the NP, as shown in Figure 2.2. Once the drug has been administered, external magnetic field guides the complex to the specific tumor. The drug is released by enzyme activity or by changes in pH, temperature, or osmolality (Tartaj et al., 2003; Chatterjee et al., 2014).

Common drug delivery materials including liposomes (Al-Jamal and Kostarelos, 2011), micelles (Ma et al., 2013), organic polymers (Yang et al., 1975), dendrimers (Patri et al., 2005), and CDs (Sun et al., 2012) have been developed. On the one hand, these materials have addressed some problems caused by small-molecule drugs to some degree. On the other hand, the accumulation of these materials within malignant lesions is generally attributed to passive targeting as a consequence of enhanced permeability and retention. An interesting tool being developed today to be utilized in tumor diagnosis is RNANPs (Zhou et al., 2011).

Biological molecules like proteins, antibodies, nucleic acids have many attributes that make them highly suitable for nanotechnology applications. For example, proteins fold into precisely defined three-dimensional shapes, and nucleic acids assemble according to well-understood rules. Antibodies are highly specific in recognizing and binding their ligands, and biological assemblies such as molecular motors can perform transport operations. From the tripeptide glutathione (cellular antioxidant) to oligopeptides (hormones) and polypeptides (proteinaceous enzymes), the peptides of various lengths play vital metabolic roles. These peptides need to aggregate or, more specifically, self-assemble into superstructures to perform their cellular roles. The result is the self-assembly of peptides, like actin, to form the elongated fibrillar structures of the cytoskeleton. Collagen is an important component of cells and tissues both. The same peptide molecules are assembled due to molecular recognition, binding them together through noncovalent interactions, namely, electrostatic interactions, hydrogen bonding, and van der Waals interactions. Simple peptide molecules can hence self-assemble into much more complex and functional superstructures, which inspires efforts to design more of such peptides for a wide range of biomedical applications.

The self-assembly hierarchy of biological materials begins with monomer molecules (e.g., nucleotides and nucleosides, amino acids, and lipids), which form polymers (e.g., DNA, RNA, proteins, and polysaccharides), then assemblies (e.g., membranes, organelles), and finally cells, organs, organisms, and even populations (Rousseau and Jelinski, 1991). Currently, research is going on developing chips based on the base pairing of DNA to build molecularsized, complex, three-dimensional objects. Seeman and coworkers have reported the formation of complex 2-D and 3-D periodic structures with defined topologies. DNA is ideal for building molecular nanotechnology objects, as it offers synthetic control, predictability of interactions, and well- controlled “sticky ends” that assemble in a highly specific fashion.

DNA chips are currently widely used in scientific, biomedical research. The chips comprise an inert support, which carries microarrays of hundreds to thousands of single-strand DNA molecules with different base sequences. DNA from a tissue sample that has been labeled with a radioactive or fluorescent material can be identified on the basis of the place on the chip where it binds with the chip DNA. Similar chips are being developed for the diagnosis of leukemias (Valk et al., 2004; Lowenberg et al., 2005) and mouth and throat tumors (Roepman et al., 2005). A new nanotechnological analytical method uses quantum dots. DNA in a sample is identified on the basis of its bonding to DNA molecules of a known composition embedded in micrometer-sized polymer spheres containing various mixtures of quantum dots, each of which provides a unique spectral bar code (color code) (Han et al., 2001).

A chip to detect prostate cancer has been developed by American researchers. The chip contains around 100 cantilever sensors (micrometersized, nanometre-thick minuscule levers), coated on one side with antibodies to prostate-specific antigen (PSA), a biomarker for that disease. The bonding of PSA with a sample placed on the chip bends the cantilevers by several nanometers, which can be detected optically. This enables clinically relevant concentrations of PSA to be measured (Wu et al., 2001; Majumdar, 2002). Antibodies placed on nanowires can be used in a similar way to detect viruses, in a blood sample, for example (Patolsky et al., 2004).

Nanoscale systems can be used to facilitate the delivery of incompatible drugs. They can also be used in theranostics, in which the particle is used as a device to diagnose and treat the disease at the same time (Shi et al., 2010). These techniques are also used for the liberation of pharmacological agents against several diseases, such as bacterial infection (Kim et al., 2004), inflammations (Camenzind et al., 1997), and principally cancer (Anma et al., 2012), among others. They are also being investigated as a tool for the delivery of drugs through the blood-brain barrier. Combining the delivery systems with contrast agents, fluorescent or radioactive substances, also makes it possible to use imaging techniques to monitor how successful the selective transport to the destination has been (Yong et al., 2007; Quintana et al., 2002). Once it has reached the target area, the active substance has to be released from the carrier at the correct rate. This can occur spontaneously by gradual diffusion, in combination with the delivery system’s degradation or otherwise. It may also occur as a result of special conditions at the destination, such as a different acidity level (Hong et al., 2002), salt concentration, temperature, or the presence of certain enzymes. The accumulation of the delivery system and/or the release of the active substance at the right place can also be controlled from outside by influencing conditions in the target organs or tissues by means of magnetic fields (Alexiou et al., 2003; Saiyed et al., 2003), ultrasonic vibrations (Nelson et al., 2002), or heat (Kong et al., 2001).

The drug delivery systems require longer their residence time of the drug in the blood accumulation in the target tissues; availability of sufficient active substance and longer shelf life allow their storage and distribution. Besides acting as a delivery system, in some cases, NPs can act as an active substance. Once they have found then way through the bloodstream into a tumor, or have been injected directly into it, metal-containing NPs can be heated using near-infrared radiation (Sharrna et al., 2012) and oscillating magnetic field (Hirch, 2003) so that the tumor cells die. These cells can then be killed by using near-infrared radiation to heat the tubes.