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Given the fact that malignant cells proliferate more rapidly than normal cells, damage to the cancer cells is anticipated to be markedly greater than normal cells. However, cancer cells generate chemoresistance mechanisms within the tumor microenvironment, while undesired toxicity may occur in the normal cells. For example, in colorectal cancer (CRC), there exist well-described sequences of mutational events that evince the shift of normal colon epithelium to premalignant adenoma and malignant adenocarcinoma. These events are 1) loss of the function of the adenomatous polyposis coli (APC) gene (encoding a protein involved in cell adhesion and transcription) in up to 85% of all cases of CRC, 2) mutation of KRAS (a GTP-ase that controls cell proliferation) in 50–60% of all cases of CRC, and 3) downregulated expression of the cell-adhesion transmembrane glycoprotein E-cadherin in almost 50–60% of all cases of CRC. Mutations in the mismatch-repair genes MLH1 and MSH2 contribute to genetic instability. Besides, there exist a number of genes alterations leading cells toward remodeling that include: 1) SMAD4 involved in the transforming growth factor signal transduction suppressing epithelial-cell growth, 2) INK4A involved in the retinoblas‐ toma tumor-suppressor pathway, and 3) TP53 alterations increasing the resistance of cancer cells to apoptosis [1]. Similar molecular/cellular alterations occur in various solid tumors, highlighting the intricacy of biological events leading to initiation and progression of malignancies. Therefore, necessity for development and advancement of more effective modalities targeting such genetic changes is perceptible to achieve successful cancer treatment and cure. After decades of disappointment, targeted therapy of cancer has been advanced by integration of immunotherapy as well as gene and cell therapy. As proof-ofconcept, recent clinical trials (e.g., anti-CTLA4 antibody, ipilimumab) have shown signifi‐

The challenge to comprehend the physiology as well as cell biology of the blood-brain barrier (BBB) began with Ehrlich and Goldman’s experimental observations that the central nervous system (CNS) is not stained by intravascular vital dyes. These studies provided the first evidence of the presence of an obstructing barrier between blood and brain. Later on, researchers like Friedemann (1942) used basic highly lipid soluble dyes to cross the BBB in order to show the brain penetration of the dyes by direct transport across the cerebral microvasculature. In 1941, Broman presented his observations upon the existence of two different barrier systems within the brain: the BBB at the cerebral microvasculature, and the blood-CSF barrier at the choroid plexus. It is now clear that in fact three main barrier layers at the interface between blood and tissue protect the CNS: the endothelium of brain capillaries, and the epithelia of the choroid plexus (CP) and the arachnoid (Abbott, 2005; Engelhardt, 2006).

To date, both viral and nonviral vectors have been exploited for delivery of gene-based therapies to target cells/tissues. Despite high efficiency of the viral vectors (e.g., retroviruses and adenoviruses), these vectors appear to be immunogenic and potentially harmful when used in clinical gene therapy protocols (Ferber, 2001b). Besides, the preparation and purification of the viral vectors appear to be laborious, cost-prohibitive and not amenable to industrial-scale manufacture. Nonviral vectors such as cationic lipids (CLs) and cationic polymers (CPs) have been categorized as advanced materials and their low immunogenicity, lack of pathogenicity, and ease of pharmacologic production continue to make them attractive alternatives to viral vectors (Medina-Kauwe et al., 2005). However, these vectors may also suffer from relatively low levels of gene transfer compared to viruses. Thus, the drive to advance these vectors continues resulting in considerable progresses in improved transfection efficiency. Nonviral vectors (in particular cationic gene delivery systems) are able to bind and enter the target cells, however they yield low gene expression. No substantial information is available on interactions of these vectors with cellular biomolecules. Since these medicaments tend to act at genomic levels, thus understanding the genomic impacts of the nonviral vectors may help develop more efficient gene delivery systems. Nonetheless, this needs recruitment of high throughput screening methodologies. To date, exploitation of the “omics” concepts (e.g., genomics, proteomics and metabolomics) is going to change the face of pharmacotherapy towards significantly more advanced and efficient pharmaceuticals (e.g., gene based nanomedicines) with minimal adverse consequences (Aardema & MacGregor, 2002). Enormous efforts have also been devoted for application of the global gene expression profiling in pharmacologic and toxicological investigations. The gene expression profiling technology has been primarily exploited for identification of underlying mechanisms for toxicity of pharmaceuticals and their genomic signatures, by which the safety liabilities can be determined and manifestations of undesired genotoxicity can be prohibited (Suter et al., 2004; Yang et al., 2004). This methodology can be successfully used for the discovery and development of any chemicals and pharmaceuticals including gene delivery nanosystems. The main focus of the current book chapter is to provide some useful information about “genocompatibility” and

Invention of microarray technology in the early 1990s revolutionized the genomic research, where it was exploited for global gene expression profiling through screening the expression of thousands of genes simultaneously (Watson et al., 1998). Northern blotting and reverse transcription polymerase chain reaction (RT-PCR) which were the traditional techniques for monitoring changes in mRNA levels were replaced with high density arrays, which proved to impart comprehensive data and to be better in the course of time. Nowadays, microarrays are used for genotyping, large scale single nucleotide polymorphism analysis, comparative genomic hybridizations, identification of new genes, establishing genetic networks and as a more routine function, gene expression profiling (Bednar, 2000). Providing a unique tool for the determination of gene expression at transcriptomic level, it confers simultaneous measurement of large fractions of the genome which can facilitates the recognition of specific gene expression patterns associated with a certain disease or a specific pharmaceutical. Detection of the inimitable genomic signature of any active compound is deemed to be another important application of microarray technology, upon which “intrinsic genomic impacts” of any pharmacologically active agent can be clarified. And presumably, such toxicity predication may promise notable information about each individual resulting in unique patterns of gene expression that, in turn, exhibit individual specific responses to a particular toxic substance. Basically, the discovery of diagnostic biomarkers has been the most promising feature of microarrays up to now and microarray technology has shown a great potential in predicting gene function and tracking the interactions among genetic networks too (Xiang & Chen, 2000). Microarray methodology has also been applied for analysis of proteins and metabolites, which are the principle controllers of gene expression, to verify the results at the molecular level. This in turn can extend our understanding of gene expression patterns and molecular pathways even though other techniques such as NMR, mass spectroscopy, gas and liquid chromatography can be employed for metabolite profiling. Having exploited such techniques, for example, the identity and quantity of different molecules can be determined in the CSF, urine or any other biological sample. Thus, by merging the classical techniques with new high-density microarray, the “omics” technology has been devised and