157ISSN 1473-7140© 2009 Expert Reviews Ltd10.1586/14737140.9.2.157www.expert-reviews.com

Editorial

Expanding role of nanotechnology in the management of colorectal cancerExpert Rev. Anticancer Ther. 9(2), 157–159 (2009)

“Nanotechnology appears to be a savior on the horizon in developing such multi-tasked systems, particularly at an atomic

or molecular level.”

Colorectal cancer is the second most com-mon cancer diagnosed in the UK, with the incidence remaining stable for over a decade. Each year, more than 36,500 people are diagnosed with this neoplasm and there is an overall 52% 5-year survival rate for patients. When diagnosed at the earliest stage (only 40% of patients), the 5-year survival rate rises dramatically to 82% [1,101].

“Gadolinium-based and iron oxide-based nanoparticles have been used to enhance MRI for

targeted imaging.”Surgery, chemotherapy and radiot herapy

are the standard treatment parameters available but treatment modalities are still substandard. Recurrence rates after surgi-cal intervention can be as high as 29% [2] and chemotherapy and radiotherapy effi-cacy has not dramatically improved over the last 5 years, often giving rise to non-specific distribution of the anti-tumor agents, with poor delivery at inadequate concentrations in the former and collateral damage in the latter. Another obstacle is the development of multi drug resistance, which can result in relapse and failure of tumor mass reduction.

There is, therefore, an unmet clinical requirement for image-based detection and targeted treatment delivery systems, and efforts are constantly being made to develop technology that would improve sensitivity and specificity in the diagno-sis and treatment of colorectal cancer. Nanotechnology appears to be a savior on the horizon in developing such multi-tasked systems, particularly at an atomic or molecular level.

Recently, great strides have been made in the development and advancement of nano technology, with the USA investing approximately US$1.4 billion into this technology in 2008 [102]. Its application in the medical field is rapidly increasing, particularly in the diagnosis and treatment of various cancers.

What is nanotechnology?Nanotechnology refers to the scientific field that deals with the creation, manipu-lation and utilization of engineered, man-made, functional particles at the nanoscale dimension (10-9 m).

Nanomedicine is the application of nano-structures and nanodevices in the diagno-sis, treatment and prevention of disease in human biological systems.

Nanotechnology in diagnosis of colorectal cancerAt present, the use of circulating contrast media in various conventional imaging modalities is broadly untargeted. The contrast agent is employed to enhance appearance and differentiate anatomical structures. Developments in nanotechnol-ogy have resulted in new methods of imag-ing with tumor-targeted contrast agents that increase sensitivity and specificity. Gadolinium-based and iron oxide-based nanoparticles have been used to enhance MRI for targeted imaging. Advancement in the technology has made it possible to conjugate a targeting molecule on nano-particles that can be directed to the recep-tor on the tumor surface. Current research has discovered an intestinal receptor for bacterial diarrheagenic heat-stable entero-toxins (STs), known as guanylyl cyclase C

Asif I HaqConsultant Colorectal Surgeon, Kings College Hospital, London, UK

Tel.: +44 208 502 1762

Fax: +44 208 502 1762

asifhaq7@gmail.com

Charlie AllenResearch Fellow in Surgery, Kings College Hospital, London, UK

Tel.: +44 208 502 1762

Fax: +44 208 502 1762

kkma2042@ doctors.org.uk

Philippe GrangeConsultant Urological Surgeon, Kings College Hospital, London, UK

Tel.: +44 208 502 1762

Fax: +44 208 502 1762

philippe.grange@ kch.nhs.uk

Manit AryaAuthor for correspondence Post-CCT Honorary Fellow in Urological Surgery, King’s College Hospital, London, UK

Tel.: +44 208 502 1762

Fax: +44 208 502 1762

manit_arya@hotmail.com

Expert Rev. Anticancer Ther. 9(2), (2009)158

Editorial Haq, Allen, Grange & Arya

(GCC), which is selectively expressed in both normal intestinal mucosa and colo rectal tumor cells, but not in extragastrointesti-nal cells and tumors [3]. Studies are ongoing to incorporate iron oxide into nanoparticles specifically targeting GCC via STs, which would enhance in vivo diagnosis with MRI [4]. An example of MRI enhancement using iron oxide nanoparticles, which is already in clinical use, is in its application for the staging of nodal disease in prostate cancer [5].

Another potential developing technology is the enhancement of colonoscopy using near-infrared fluorescence (NIRF) imag-ing agents. The technique is based on the application of quan-tum dots, which are nanoparticles with light-emitting proper-ties. Laboratory studies have demonstrated that it is possible to visualize tumor-associated lysosomal protease activity in a murine model of colon cancer. In one study, Weissleder et al. described the technique whereby engineered NIRF probe car-riers were injected into the circulation [6]. Tumor vasculature is known to have enhanced permeability [7] and this resulted in leakage and accumulation of the NIRF carriers in the tumor microenvironment. The NIRF carriers were then cleaved by neoplastic protease activity, resulting in the release of previ-ously quenched photochrome. This NIRF signal could then be imaged, thereby enhancing the localization of the cancerous cells [6].

Nanotechnology in the treatment of colorectal cancerIn the context of the application of nanotechnology for thera peutic treatment, one example can be seen in targeting nanoshells for receptor-directed thermal ablation. Nanoshells are nanoparticles composed of metallic shells with dielectric cores. Experimental murine models have shown that gold–silica nanoshells, when exposed to NIR light, would induce thermal damage to sur-rounding tissues [8]. Hence, engineered gold nanoshells bound to STs, which have GCC-targeting properties, can potentially be employed to ablate colorectal cancer cells when NIR radiation is applied. Nevertheless, thick and vascularized human tissue, such

as the liver, poses a potential problem, as higher levels of infrared energy can be absorbed compared with the thinner animal mod-els. Studies are currently in progress to validate this method for clinical use in humans.

Active targeting within other branches of medicine has pro-gressed to clinical trials. One such example is the application of targeted nanoparticles as a drug-delivery system for the treatment of primary hepatocellular carcinoma [9]. Another study has shown that it is possible to overcome drug resistance using engineered nanoparticle drug delivery, such as in the treatment of Kaposi sarcoma, using liposomal doxorubicin [10].

ConclusionThe development of cancer nanotechnology will certainly lead to an increased application of molecular imaging and targeted therapy. The specific manner of the targeting nanoparticles would result in enhanced detection of micrometastases and those tumors in their early stages before they become incurable by conven-tional methods. In addition, the therapeutic approach to cancer treatment could be individualized and targeted specifically to the cancer cells, hence collateral damage to surrounding tissue could be minimalized.

In fact, progression in nanotechnology could revolutionize medicine, the same way that DNA discovery has transformed and modernized diagnosis and treatment of diseases. Critics have raised concerns about the impact of the technology on human health. The Office of Science and Technology in the UK has recommended more research into the toxicology aspect of the technology. Nevertheless, it is anticipated that further develop-ment in nanotechnology will help to improve the survival rates of patients with colorectal cancer, whereby the disease could be discovered earlier and treated in a targeted manner. It remains a challenge to researchers to develop and apply this technology in a way that would be both safe and more efficient.

Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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“...progression in nanotechnology could revolutionize medicine, the same way that DNA

discovery has transformed and modernized diagnosis and treatment of diseases.”

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EditorialExpanding role of nanotechnology in the management of colorectal cancer

Weissleder R, Tung C, Mahmood U, 6

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Websites

Ries LAG, Melbert D, Krapcho M 101 et al. SEER Cancer Statistics Review, 1975–2004, National Cancer Institute. Bethesda, MD. Based on November 2006 SEER data submission http://seer.cancer.gov/csr/1975_2004/

National Nanotechnology Initiative FY 102

2008 Budget Supplement http://nano.gov