期刊
BIOCONJUGATE CHEMISTRY
卷 26, 期 2, 页码 294-303出版社
AMER CHEMICAL SOC
DOI: 10.1021/bc5005679
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资金
- National Institutes of Health [R00 CA153916, R01 EB019449]
- Wake Forest Institute for Regenerative Medicine
- WFU-VT SBES
- NIH [1S10RR17846]
- Thermo Electron TSQ Quantum XLS GC/MS/MS from NIH [1S10RR027940]
- Comprehensive Cancer Center of Wake Forest University NCI [CCSG P30CA012197]
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 beta-cholanamide (5 beta 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.
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