Identification and Usage of Fluorescent Probes as Nanoparticle Contrast Agents in Detecting Cancer

Manikanta   Swamy   Murahari; Mayur   C.   Yergeri

doi:10.2174/1381612811319250009

Abstract

As advancements in the field of nanoparticle imaging science are made, one of the first benefits will be in open and endoscopic conditions. There is considerable evidence indicating that the use of injected contrast agents can improve the detection of tumor margins and small metastases. New and innovative targeting and contrast agents including small molecules, antibodies and nanoparticles have to be developed for a broad range of tumor types such as breast, brain, pancreatic, and ovarian cancers. At present, a number of organic dye molecules have been approved for human use including (1) indocyanine green (ICG), a near-infrared fluorescent dye; (2) fluorescein, a green fluorescent dye; (3) photofrin, a mixture of fluorescent protoporphyrin oligomers approved for photodynamic therapy, and (4) 5-aminolevulinic acid (ALA), a small molecule that is preferentially taken up by tumor cells leading to biosynthesis and accumulation of protoporphyrin IX, a natural fluorophore with red fluorescence emission. On the other hand, nanoparticles have not received FDA approval for clinical imaging, as this technology needs a lot of development and lot of research is being carried out in this unexplored area.

A major task is, therefore to develop biocompatible and nontoxic nanoparticle contrast agents with the potential for FDA approval and human use. Such agents need to show improved sensitivity and specificity for tumor imaging in comparison with small-molecule-dyes. In this regard, it is highly promising to develop smart or activatable nanoparticles with improved pharmacokinetic, tumor targeting and organ clearance properties, based on the use of natural, biodegradable polymers (dextran and heparin). Dextran-based particles are sensitive to pH, and can be rapidly broken down under acidic conditions. Under neutral or slightly basic conditions, on the other hand, the dextran nanoparticles are stable and are able to circulate systemically in blood for 14 to 15 hours. In contrast, self-assembled heparin nanoparticles have much shorter blood circulation half-lives (about 60-80 min). For intra-operative use, this short circulation time could be beneficial because the probes will be cleared from the body quickly, so that surgical operations and treatment can start without much delay or waiting. For near-term clinical applications, it is important that both the dextran and heparin particles are able to trap as FDA-approved dye (such as indocyanine green), leading to new class of imaging contrast agents with improved bio distribution and photo physical properties. This class of nanoparticle contrast agents could also be conjugated with tumor targeting ligands such as folate, Epidermal Growth Factor (EGF), or RGD (recognition sequence for integrins that contains Arg-Gly-Asp attachment site) for improved sensitivity and specificity in perfect cancer imaging technique agents. This review article actually highlights the new developments occurring in this area of imaging techniques in cancer research and the author himself is using the technique for developing newer fluorescent molecules for molecular imaging using nanotechnology.

Keywords: Nanoparticles, cancer, contrast agents, quantum dots, dextran, heparin.

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