Indocyanine Green-Loaded Nanoparticles for Image-Guided Tumor Surgery

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• 作者：Tanner K. Hill ; Asem Abdulahad ; Sneha S. Kelkar ; Frank C. Marini ; Timothy E. Long ; James M. Provenzale ; Aaron M. Mohs
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：February 18, 2015
• 年：2015
• 卷：26
• 期：2
• 页码：294-303
• 全文大小：532K
• ISSN：1520-4812

文摘

Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5尾-cholanamide (5尾CA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone.