Mixed Micelles Of Triblock Copolymers Enhance Delivery Of Indocyanine Green For Fluorescent Tumor Imaging

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The goal of this study is to develop formulations for non-invasive, near-infrared detection of tumors. Indocyanine green (ICG) is an FDA-approved near-infrared (NIR) imaging agent that is clinically used for angiography and evaluation of liver function. ICG could potentially be used as a NIR fluorescence imaging agent for shallow tumors such as breast cancers. To fulfill this potential, formulations that improve the stability of ICG and direct its accumulation in tumors are necessary. We have previously described Pluronic F127 copolymer micelles that stabilize ICG, enhance its stability, and facilitate tumor accumulation in vivo after systemic administration. A major advantage of Pluronic F127 is its temperature-sensitive behavior that results in more stable micelle formulations at body temperature. However, Pluronic F127 micelles are not stable at room temperature, making micelle preparation and handling challenging. We hypothesized that mixed micelles formed from both Pluronic F127 and a temperature insensitive triblock copolymer composed of poly(ethylene oxide) and poly(3-hydroxybutyrate) (PEO-PHB-PEO), would result in micelles that are both easy to formulate at room temperature and that demonstrate increased stability at body temperature. Micelle formulations with various ratios of Pluronic F127: PEO-PHB-PEO were prepared and loaded with ICG. The micelle stability was determined by assessment of critical micelle concentration measurements, and time-course fluorescence assays were conducted to assess the ability of each micelle formulation to stabilize ICG fluorescence in buffer conditions. The ICG-loaded micelles were administered to tumor-bearing mice by tail vein injection and tumor localization was monitored by non-invasive fluorescence imaging in live mice. The polymer ratio used in micelle formulation was found to play a significant role in the ability of each preparation to stabilize ICG fluorescence Mixed micelles were found to enhance the stability of ICG fluorescence in buffer conditions, and CMC was shown to be dependent on polymer ratios. In vivo, mixed micelles were found to be more effective at maintaining ICG fluorescence in the bloodstream and achieved higher fluorescence signals in the tumor tissues compared with either PEO-PHB-PEO or Pluronic 127 micelles. These results suggest that the mixed micelle formulations offer a promising route to stabilizing these nanoparticles for improved delivery of NIR fluorescent contrast agents to tumors for imaging applications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5293. doi:10.1158/1538-7445.AM2011-5293