Brain Tumor Visualization with Fluorescent Nanoparticles

Background: Use of near-infrared (NIR) fluorescent nanoparticles has promise as an aide in visualizing brain tumor localization during surgery. Cancers often develop defective and leaky vasculature during angiogenesis as well as impaired lymphatic drainage system, allowing macromolecules and nanoparticles to be effectively delivered and retained to tumor tissue. Commonly referred to as the enhanced permeability and retention (EPR) effect, this has become the gold standard in anti-cancer drug design and delivery. Here we look at accumulation of polymeric nanoparticles that have been loaded with DiR (a near-infrared dye) at different points in tumor progression in mouse brains that have been implanted with glioma tumor cells. Methods:GL261-luc2 Cells were intracranially implanted into the striatum of healthy C57bl/6 albino mice and tumor size was monitored by IVIS imaging. At 4, 8, 12, 16, or 20 days post implantation, subjects were sacrificed 2 hours post intravenous administration of DiR loaded nanoparticles. Whole brains were harvested and sectioned into 2mm thick slices. Nanoparticle distribution was visualized by a LI-COR odyssey system and further quantified by taking tumor, peri-tumor, and healthy tissue samples and homogenizing to compare to control tissue spiked with known amounts of dye. Results:Tumor tissues were readily visualized and distinguished from healthy tissue in images captured by the LI-COR system in later stages of tumor progression (8+ days post implantation). Tumor size correlated positively with nanoparticle accumulation in tumor and peri-tumor tissue (p=0.002 and 0.048 respectively) but not with healthy tissue. Significant ratios of average nanoparticle accumulation in tumor verses healthy tissues were also quantified at approximately 5:1, 6:1, and 14:1 at days 12, 16, and 20 post implantation respectively.   Conclusion: NIR fluorescent nanoparticles are able to enhance contrast between tumor and healthy tissue as early as 2 hours post administration, demonstrating a potential use as a visual aide during surgical resection.