Florida International University, Biomedical Engineering Department, 10555 W. Flagler St., EC 2613, Miami, FL 33174, USA.
J Photochem Photobiol B. 2013 Feb 5;119:52-9. doi: 10.1016/j.jphotobiol.2012.12.008. Epub 2012 Dec 28.
This study reports the preparation and characterization of IR820-chitosan conjugates that have potential multifunctional imaging-hyperthermia applications in cancer. The conjugates were formulated by covalentcouplingofchitosan to a carboxyl derivatized IR820, and studied for optical imaging and hyperthermia applications. IR820-chitosan conjugates were able to generate heat upon exposure to 808nm laser and produce hyperthermic cell growth inhibition in cancer cell lines MES-SA, SKOV-3 and Dx5. The level of cell growth inhibition caused by hyperthermia was significantly higher for IR820-chitosan compared to IR820 in MES-SA and Dx5 cells. Fluorescent microscope images of these cancer cell lines after 3-h exposure to 5μM IR820-chitosan showed that the conjugates can be used for in vitro near-infrared imaging. In an in vivo rat model, the conjugates accumulated in the liver after i.v. injection and were excreted through the gastrointestinal tract, demonstrating a different biodistribution when compared to the free dye. The accumulation of these conjugates in bile with subsequent gastrointestinal excretion allows for potential applications as gastrointestinal contrast agents and delivery vehicles. This formulation can potentially be used in multifunctional cancer theranostics.
本研究报告了 IR820-壳聚糖缀合物的制备和表征，该缀合物在癌症的多功能成像-热疗中有潜在的应用。该缀合物通过壳聚糖与羧基衍生的 IR820 的共价偶联来制备，并研究了其在光学成像和热疗中的应用。IR820-壳聚糖缀合物在暴露于 808nm 激光时能够产生热量，并在 MES-SA、SKOV-3 和 Dx5 癌细胞系中产生高热抑制细胞生长。与 MES-SA 和 Dx5 细胞中的 IR820 相比，热疗引起的细胞生长抑制水平在 IR820-壳聚糖中要高得多。这些癌细胞系在暴露于 5μM IR820-壳聚糖 3 小时后的荧光显微镜图像表明，该缀合物可用于体外近红外成像。在体内大鼠模型中，缀合物经静脉注射后在肝脏中积累，并通过胃肠道排泄，与游离染料相比表现出不同的生物分布。这些缀合物在胆汁中的积累随后通过胃肠道排泄，使其可作为胃肠道造影剂和递药载体。这种制剂有可能用于多功能癌症治疗。
