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January 17, 2011

Advances in the field of nanooncology - nanotechnology against cancer

BMC Medicine - Advances in the field of nanooncology (nanotechnology against cancer)

Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important chapter of nanomedicine. Nanobiotechnology has refined and extended the limits of molecular diagnosis of cancer, for example, through the use of gold nanoparticles and quantum dots. Nanobiotechnology has also improved the discovery of cancer biomarkers, one such example being the sensitive detection of multiple protein biomarkers by nanobiosensors. Magnetic nanoparticles can capture circulating tumor cells in the bloodstream followed by rapid photoacoustic detection. Nanoparticles enable targeted drug delivery in cancer that increases efficacy and decreases adverse effects through reducing the dosage of anticancer drugs administered. Nanoparticulate anticancer drugs can cross some of the biological barriers and achieve therapeutic concentrations in tumor and spare the surrounding normal tissues from toxic effects. Nanoparticle constructs facilitate the delivery of various forms of energy for noninvasive thermal destruction of surgically inaccessible malignant tumors. Nanoparticle-based optical imaging of tumors as well as contrast agents to enhance detection of tumors by magnetic resonance imaging can be combined with delivery of therapeutic agents for cancer. Monoclonal antibody nanoparticle complexes are under investigation for diagnosis as well as targeted delivery of cancer therapy. Nanoparticle-based chemotherapeutic agents are already on the market, and several are in clinical trials. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level, which is facilitated by nanobiotechnology. Nanobiotechnology will facilitate the combination of diagnostics with therapeutics, which is an important feature of a personalized medicine approach to cancer.




Gold nanoparticles for cancer diagnosis

By attaching monoclonal antibodies (mAbs), which can recognize a specific cancer cell, to gold nanoparticles or nanorods the "heating phenomenon" can be used in cancer detection. This acoustic signal gives valuable information about the presence of cancer cells. Gold nanoparticles conjugated to anti-epidermal growth factor receptor (anti-EGFR) mAbs specifically and homogeneously bind to the surface of the cancer cells with 600% greater affinity than to the noncancerous cells. The particles that worked the best in the El-Sayed et al. study were 35 nm in size.

Quantum dots for molecular diagnosis of cancer

There is considerable interest in the use of QDs as inorganic fluorophores, owing to the fact that they offer significant advantages over conventionally used fluorescent markers. For example, QDs have fairly broad excitation spectra, from ultraviolet to red, that can be tuned, depending on their size and composition.

Nanotechnology for detection of cancer biomarkers

Any specific molecular alteration of a cell on the DNA, RNA, metabolite or protein level may be referred to as a molecular biomarker. From a practical point of view, the biomarker would specifically and sensitively reflect a disease state and could be used for diagnosis as well as for disease monitoring during and following therapy [6]. Currently available molecular diagnostic technologies have been used to detect biomarkers of various diseases such as cancer. Nanotechnology has further refined the detection of biomarkers. The physicochemical characteristics and high surface areas of nanoparticles make them ideal candidates for developing platforms for harvesting biomarkers. Some biomarkers also form the basis of innovative molecular diagnostic tests.

A magnetic nanosensor technology is up to 1,000 times more sensitive than any technology now in clinical use, can detect biomarker proteins over a range of concentrations three times broader than any existing method and is accurate regardless of which bodily fluid is being analyzed. The nanosensor chip also can search for up to 64 different proteins simultaneously and has been shown to be effective in early detection of tumors in mice, suggesting that it may open the door to significantly earlier detection of even the most elusive cancers in humans. The magnetic nanosensor can successfully detect cancers in mice when levels of cancer-associated proteins are still well below concentrations detectable using the current standard method, the enzyme-linked immunosorbent assay. The sensor also can be used to detect biomarkers of diseases other than cancer.

Investigating the potential for capturing circulating tumor cells
A method has been described for magnetically capturing circulating tumor cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumor cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging.

Imaging applications of nanobiotechnology in cancer

Highly lymphotropic superparamagnetic iron oxide nanoparticles (SPIONs), measuring 2 to 3 nm on average (Combidex, Advanced Magnetics, Cambridge, Mass, USA), gain access to lymph nodes by means of interstitial lymphatic fluid transport. SPIONs have been used in conjunction with high-resolution MRI to reveal small and otherwise undetectable lymph node metastases. In patients with prostate cancer who undergo surgical lymph node resection or biopsy, MRI with lymphotropic SPIONs can identify all patients with nodal metastases. This is important for the management of cancer, but is not possible with conventional MRI alone. Occult lymph node metastases in patients with prostate cancer have been identified by this technique prior to salvage radiation therapy

Nanotechnology-based drugs for cancer
Approximately 150 drugs in development for cancer are based on nanotechnology.




Nanooncology has a promising future, and further advances are anticipated in the next 5 years. It is feasible to use molecular tools to design a miniature robotic device, a nanobot, that can be introduced in the body to locate and identify cancer cells and finally destroy them. The device would have a biosensor to identify cancer cells and a supply of anticancer substance that could be released on encountering cancer cells. A small computer could be incorporated to program and integrate the combination of diagnosis and therapy and provide the possibility of monitoring the in vivo activities by an external device. Since there is no universal anticancer agent, the computer program could match the type of cancer to the most appropriate agent. Such a device could be implanted as a prophylactic measure in people who do not show any obvious manifestations of cancer. It would circulate freely and could detect and treat cancer at the earliest stage. Such a device could be reprogrammed through removal control and enable a change of strategy if the lesion encountered is other than cancer

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