Hill Tanner K, Abdulahad Asem, Kelkar Sneha S, Marini Frank C, Long Timothy E, Provenzale James M, Mohs Aaron M
Virginia Tech - Wake Forest University School of Biomedical Engineering and Sciences, ‡Wake Forest Institute for Regenerative Medicine, §Department of Cancer Biology, Wake Forest University Health Sciences , Winston-Salem, North Carolina 27157, United States ;
Bioconjug Chem. 2015 Feb 18;26(2):294-303. doi: 10.1021/bc5005679. Epub 2015 Jan 16.
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-5β-cholanamide (5βCA), 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.
手术过程中检测肿瘤切缘阳性和局部恶性肿块对患者的长期生存至关重要。使用图像引导手术切除肿瘤，特别是近红外荧光成像，是一种有助于在手术部位切除所有肿瘤组织的潜在方法。在本研究中，我们展示了一系列由透明质酸（HLA）衍生的纳米颗粒，它们包裹近红外染料吲哚菁绿，称为纳米吲哚菁绿（NanoICG），以改善染料向肿瘤的递送。纳米颗粒的自组装由三种疏水基团之一的共轭驱动：氨丙基-1-芘丁酰胺（PBA）、氨丙基-5β-胆酰胺（5βCA）或十八胺（ODA）。对纳米颗粒的自组装、染料负载和光学性质进行了表征。纳米吲哚菁绿表现出淬灭荧光，可通过在混合溶剂中解聚而激活。发现纳米吲哚菁绿在生理相关浓度下无毒，且未发现暴露会抑制细胞生长。在小鼠的MDA-MB-231肿瘤异种移植模型中，使用荧光图像引导手术系统和全动物成像系统观察到纳米吲哚菁绿使肿瘤中的荧光显著增强。纳米吲哚菁绿的肿瘤对比度明显高于单独使用吲哚菁绿。
