Pharma Voice

Nanoshells, a promising alternative

Ashok Patel

Significant progress has been made in the development of new agents against cancer and new delivery technologies. Proteomics and genomics continue to uncover molecular signatures that are unique to cancer. Yet, the major challenge remains in targeting and selectively killing cancer cells while affecting as few healthy cells as possible. Nanometer sized particles have novel optical, electronic and structural properties that are not available from either individual molecules or bulk solids. When linked with tumour targeting moieties, these nanoparticles can be used to target cancer-specific receptors, tumour antigens and tumour vasculatures. Despite significant advances made over the last decade or so in developing nano-based techniques for cancer targeting, the great potential of this new generation of targeted cancer nanotherapy remains to be completely exploited.

Most of the research in this field is based on developing drug encapsulated biodegradable nanoparticles with attached targeting moieties for targeted accumulation at the cancer sites. However, the targeting capacity of nanoparticles has been found to be limited resulting in distribution of drug loaded particles to undesired sites which later leads to unwanted toxic effects associated with the drug. Some of the effects being substantial loss of hair, lack of appetite and reduced immune response. Alternate methods of cancer treatments like surgical tumour removal and radiotherapy, have their own demerits. Where surgery is limited to tumours which are accessible (epithelial tumours), radiotherapy is highly invasive to healthy tissues in the path of radiation resulting in various adverse effects. Thus, there's a pressing need to find an alternate method for cancer therapy.

Recently, nanoscientists have come up with an interesting solution to overcome drawbacks associated with traditional radiotherapy and targeted cancer chemotherapy. They have proposed a fundamentally new approach to non-chemotherapeutic cancer therapy using nanofabricated particles with unique tunable optical properties collectively known as nanoshells.

Nanoshells and cancer therapy

Nanoshell particles constitute a special class of nano-composite materials. They consist of concentric particles, in which particles of one material (core) are coated with a thin layer of another material (shell) using specialised procedures. The core typically comprises of a dielectric material (like silica) coated with thin metallic layer (usually gold) which forms the shell. Nanoshell particles are highly functional materials with tailored properties, which are quite different than the core or the shell material. Indeed, they show modified and improved properties than their single component counterparts or nanoparticles of the same size. Therefore, nanoshell particles are preferred over nanoparticles. Their properties can be modified by changing either the constituting materials or core-to-shell ratio.

The term nanoshell is used specifically because the thickness of the shell is around 1-20 nm. By carefully choosing the core-to-shell ratio, it is possible to design novel nanoshell structures, with optical resonance extending from the visible to approximately 3 µm in the infrared. This spectral region includes the 800-1300 nm "water window" of the near infrared, a region of high physiological transmissivity. It has been demonstrated as the spectral region best suited for optical bio-imaging and bio-sensing applications. By controlling physical parameters of the nanoshells, it is possible to engineer nanoshells which strongly absorb light in the near IR region and in the process, convert it into thermal energy, thereby raising the surrounding temperature. This photo-thermal property of nanoshells, combined with nano targeting principles, can be effectively exploited for cancer treatment.

When these nanoshells are inserted in the body, they get attached to diseased cells and hence, can be imaged. Once the tumour is located, it is irradiated externally using laser source with the resonance wavelength of the nanoshells. This leads to localised heating of the tumour which destroys it photo-thermally. In laboratory cultures, the potential of photo thermal cancer therapy has been fully evaluated and it was found that the heat generated by the light-absorbing nanoshells had successfully killed tumour cells while leaving neighbouring cells intact. Since the optical resonance of nanoshell is tuned to the near infra-red region, which is physiologically safe and can penetrate up to a few centimeters deep, it is proposed that the in-vitro success of cancer therapy by nanoshells can be extended to not only skin or surface type cancers but also to tumours residing in deeper tissues. The optical properties of gold nanoshells, when coupled with their biocompatibility and ease of bio-conjugation, render these nanoparticles highly suitable for targeted therapeutic applications. Thus, nanoshells offer an effective and relatively safer alternative for targeted cancer nanotherapy.

(The writer is a Senior Research Fellow, PhD Tech Student, University Institute Of Chemical Technology, Mumbai)