Title:Identification and Usage of Fluorescent Probes as Nanoparticle Contrast Agents in Detecting Cancer
Volume: 19
Issue: 25
Author(s): Manikanta Swamy Murahari and Mayur C. Yergeri
Affiliation:
Keywords:
Nanoparticles, cancer, contrast agents, quantum dots, dextran, heparin.
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.
