**6. Conclusion**

538 Non-Viral Gene Therapy

mAbs specifically and homogeneously bind to the surface of the cancer cells with 600% greater affinity than to the noncancerous cells. This specific and homogeneous binding is found to give a relatively sharper surface plasma resonance (Hinz et al. 2006) absorption band with a red shifted maximum compared to that observed when added to the noncancerous cells . Surface plasma resonance scattering imaging or SPR absorption spectroscopy generated from antibody conjugated gold nanoparticles may be useful in molecular biosensor techniques for the diagnosis and investigation of cancer cells *in vivo* and

These inorganic nanoparticles represent a different class of nanoparticles that are usually much smaller, 5–40 nm and they do not have the flexibility observed in liposomes and polymeric nanoparticles. Inorganic nanoparticles have made their appearance in cancer therapy during the last decades in a number of applications. The main type of inorganic nanoparticles—the iron oxide nanoparticles, has been used for imaging tumor (Wang and Thanou 2010). The main advantage of magnetic nanoparticles is their ability to be visualised by Magnetic Resonance (MR) imaging. Additionally, iron oxide nanoparticles can be guided to target sites (i.e. tumor) using external magnetic field and they can be also heated to provide hypethermia for cancer therapy. Yu et al. reported thermally crosslinked superparamagnetic iron oxide nanoparticles that could carry a Cy5.5 near infra-red probe (dual imaging) and doxorubicin for the imaging and treatment of cancer. The nanoparticles substantially diminished tumor size and provided the proof of concept that they can combine several modalities for maximum antitumor effect (Yu et al. 2010). Magnetic nanoparticles have been used in the development of dual purpose probes for the *in vivo* transfection of siRNA. The iron nanoparticles deliver siRNA at the same time as imaging their own accumulation in tumor sites. Hence, multifunctional nanoparticles have emerged that are capable of cancer targeting and simultaneous cancer imaging and

Metal nanoshells are another class of nanoparticles with tunable optical resonances. Metal nanoshells consist of a spherical dielectric core nanoparticle, in this case silica, which is surrounded by a thin metal shell, such as gold. These particles possess a highly tunable plasmon resonance, a resonant phenomenon whereby light induces collective oscillations of conductive metal electrons at the nanoshell surface. Nanoshells derived from gold provide an attractive system for imaging applications owing to the established ease of preparation, chemical inertness, good biocompatibility, and surface functionalization. Further, nanoparticle based near infrared imaging (NIR) is steadily presenting itself as a powerful diagnostic technique with the real potential to serve as a minimally invasive, nonionizing method for sensitive, deep tissue diagnostic imaging that are not prone to the rapid photobleaching and instability of their organic counterparts. NIR laser treatment of the bulk tissue selectively heats and destroys the nanoshell-laden tumor regions within the tissue, while leaving surrounding tissue intact. Nanoshells are currently evaluated in a number of clinical settings after a 5-year period of intensive preclinical development. Such development of nanoshells included the combination of nanoshells with cancer antibodies. Anti-HER2 antibody conjugated onto nanoshells provides the potential of combining antibody therapy with imaging and hyperthermia. NIR dye-encapsulating nanoparticles also demonstrate improved optical performances compared to unencapsulated organic fluorophores. Specifically, the encapsulation shields the dye molecules from unfavorable environmental influences that normally hinder fluorescence signals, thereby enhancing quantum yields, emission brightness, and fluorescent lifetime. While, at present, these NIR

*in vitro*.

therapy.

With the understanding of the genetic origins of certain cancers, an entirely new approach to the treatment of this disease has evolved, employing nanoparticle-based gene therapy. Numerous nanoparticle based cancer gene therapy strategies are already in clinical trials. The key to the success of any new therapeutic is to maximize safety without compromising efficacy, which has led to growing interest in non-viral gene delivery systems (such as liposomes) over the viral gene delivery systems. Grafting biorecognition molecules (ligands, antibodies) onto the nanoparticles (i.e active targeting) aims to improve targeting by specific cell uptake and using hydrophilic polymer coating, PEG, which aims to further enhance biocompatibility. To overcome other challenges of gene therapy, such as escape from endosome and other nuclear and cytosolic barriers, next generation vectors are being designed with use of gene regulatory elements (promoters and enhancers) to restrict gene expression to specific cells, along with nuclear localization signal peptides for nuclear targeting.

There has been substantial interest in dual purpose nanoparticle based gene therapy for both diagnostic (imaging) and therapeutic purposes (drug/gene delivery). Newer technologies for cancer detection/diagnosis using metallic and semiconducting nanoparticles are also under intense investigation. These nanoparticles for *in vivo* application targeting cancer are amenable to different size structures and possess tunable properties. Quantum dots possess unique size- and composition- dependent optical and electrical properties. In addition to quantum dots, carbon nanotubes, paramagnetic nanoparticles, nanoshells and nanosomes represent just a few of these novel technologies, used for both diagnostic and delivery purposes.

The imminent research challenge facing investigators moving forward is the expansion of the knowledge and understanding of the chemical and physical properties associated with these nanoparticle systems toward the design of superior cancer therapy modalities that maximize efficiency of treatment, while maintaining a superior safety profile.
