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'The Role of Nanodrugs for Targeted Drug Delivery in Cancer Treatment'

Nanotechnology has achieved the status as one of the critical research endeavors of the early 21century. Nanoscale devices and components are smaller than human cells (10,000 – 20,000 nmin diameter) & organelles and similar in size to large biological macromolecules such as enzyme& receptors – Hb for e.g., is approx 5 nm in diameter. While the lipid bilayer surrounding the cells are on the order of 6 nm thick. Nanoscale devices are smaller than 50 nm can easily enter most cells, while those smaller than 20 nm can transit out of blood vessels. Therefore, the size of the Nanoscale devices allows them to interact readily with biomolecules on the cell surface and within the cell, often in ways that do not alter the behavior and biochemical properties of those molecules. Such ready access to the interior of a living cell affords the opportunity for unprecedented gains on the clinical and basic frontiers. Nanotechnology research is generating a variety of constructs giving cancer researchers great flexibility in their efforts to change the paradigm of cancer diagnosis, treatment, and prevention. In this study we focused how Cancer Nanotechnology is to develop safer and more effective diagnostic and therapeutic modalities for Cancer therapy.

Introduction A nanometer is billionth of a meter, which is about 1/80,000 of the diameter of a human hair, or ten times the diameter of a hydrogen atom. It manipulates the chemical and physical properties of a substance on molecular level. Nanotechnology alters the way we think, it blurs the boundaries between physics, chemistry and biology, the elimination of these boundaries will pose many challenges and new directions for the organization of education and research.

We define nanoscience as the study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale; and nanotechnologies as the design, characterization, production and application of structures, devices and systems by controlling shape and size at the nanometer scale. These technologies have been applied to improve drug delivery and to overcome some of the problems of drug delivery for cancer treatment.

The bulk properties of materials often change dramatically with Nano ingredients. Composites made from particles of Nano-size ceramics or metals smaller than 100 nanometers can suddenly become much stronger than predicted by existing materials-science models. For example, metals with a so-called grain size of around 10 nanometers are as much as seven times harder and tougher than their ordinary counterparts with grain sizes in the hundreds of nanometers. The causes of these drastic changes stem from the weird world of quantum physics. The bulk properties of any material are merely the average of all the quantum forces affecting all the atoms. As you make things smaller and smaller, you eventually reach a point where the averaging no longer works.The properties of materials can be different at the Nanoscale for two main reasons First, nanomaterials have a relatively larger surface area when compared to the same mass of material produced in a larger form. This can make materials more chemically reactive (in some cases materials that are inert in their larger form are reactive when produced in their Nanoscale form), and affect their strength or electrical properties.Second, quantum effects can begin to dominate the behavior of matter at the Nanoscale -particularly at the lower end - affecting the optical, electrical and magnetic behavior of materials.materials can be produced that are Nanoscale in one dimension (for example, very thin surface coatings), in two dimensions (for example, nanowires and Nanotubes) or in all three dimensions(for example, Nanoparticles). The properties of materials can be different at the Nanoscale for two main reasons First, nanomaterials have a relatively larger surface area when compared to the same mass of material produced in a larger form. This can make materials more chemically reactive (in some cases materials that are inert in their larger form are reactive when produced in their Nanoscale form), and affect their strength or electrical properties.Second, quantum effects can begin to dominate the behavior of matter at the Nanoscale -particularly at the lower end - affecting the optical, electrical and magnetic behavior of materials.Materials can be produced that are Nanoscale in one dimension (for example, very thin surface coatings), in two dimensions (for example, nanowires and Nanotubes) or in all three dimensions(for example, Nanoparticles). Why Nanotechnology in CancerBold text Nanoscale devices are somewhere from 100-1000 times smaller than human cells. They are similar in size to large biological molecules such as enzymes and receptors. As an e.g. Hemoglobin, the molecule that carries oxygen in RBC is approximately 5nm in diameter. Nanoscale devices smaller than 50nm can easily enter most cells, while those smaller than 20nm can move out of blood vessels as they circulate through the body Because of their small size, Nanoscale devices can readily interact with the biomolecules on the surface of cells and inside of cells, without changing the behavior and biological properties of these molecules [1]. By gaining access to so many areas of the body, they have the potential to detect disease and deliver treatment in ways unimagined before now. And since biological processes including events that lead to cancer, occur at the Nanoscale at and inside cells, Nanotechnology offers a wealth of tools that provide cancer researchers, a new and innovative ways to diagnose and treat cancer. Nanoparticles also carry the potential for targeted and timerelease drugs. A potent dose of drugs could be delivered to a specific area but engineered to release over a planned period to ensure maximum effectiveness and the patient's safety. Because of their small size, Nanoparticles can accommodate tens of thousands of atoms or small molecules, such as Magnetic Resonance Imaging contrast agent gadolinium[2], creating the opportunities for improved detection sensitivity of diseases such as Cancer at its earliest stage.One more benefit of use of Nanoparticles in cancer is due to their surface chemistry. Modification of Nanoparticles outer layer allows a large variety of chemical, molecular, and biological entities to be covalently or otherwise bound to it. Manipulation of this corona confers advantageous properties to the particles, such as increased solubility and biocompatibility. Attaching hydrophobic polymers to the surface, such as Polyethylene glycol, greatly increases the hydration (i.e. solubility) of the Nanoparticles and can protect attached proteins from enzymatic degradation when used for in vivo application [3]. The surface addition of PEG(“pegylation”) and other hydrophilic polymers also increases the in vivo compatibility of nanoparticles. When injected intravascularly, uncoated Nanoparticles are cleared rapidly injected intravascularly, uncoated nanoparticles are cleared rapidly from the blood stream by the Reticulo Endothelial System [4]. Nanoparticles coated with hydrophilic polymers have prolonged halflives, believed to result from decreased opsonization and subsequent clearance by macrophages [5]. Nanodevices are capable of detecting cancer at its earliest stage, pinpointing its location within the body, delivering anticancer drugs specifically to malignant cells, and determining if these drugs are killing malignant cells. Nanotechnology will serve as multifunctional tools that will not only be used with any number of diagnostic and therapeutic agents but will change the very foundation of cancer diagnosis, treatment and prevention.One strategy to concentrate cancer drugs only in their target tissue is through a mechanism known as enhanced permeability and retention effect (EPR) which happens in solid tumors. In fact, the network of blood vessels in many solid tumors has been shown to differ considerably from normal vasculature and to contain gaps in which tumor cells lack close contact with perfusing vessels, which ultimately leads to increased permeability. In this situation, drug delivery systems which are usually excluded from entering into tissues can extravasate into tumors and increase drug concentration 10-fold or more than administration of the same dose of free drug. Reference [1] K .Bogumia. Kubik, M. Sugisaka, “Molecular biology to nanotechnology and Nanomedicine Biosystems” 65, 123- 138 (2002) [2] A. M., Morawski, P. M Winter, K. C.Crowder, S. D Caruthers, R. Fuhrhop, W.Scott, J.D.Robertson, D.R.Abendschein, G.M.Lanza, Wickline, Magn. Reson. Med. 51, 480-486. S. A. (2004) [3] J. M. Harris, R. B .Chess, Nat. Rev.Drug Discovery. 2, 214- 221. (2003) [4] I. Brigger, C Dubernet, P. Couveur, Adv.Drug Deliv. Rev. 54, 631-651. (2002) [5] S.M. Moghimi, Sczebeni, J. Stealth Prog.Lipid Res.42, 463-478. (2003)