Gold hybrid nanoparticles for targeted phototherapy and cancer imaging
Gold hybrid nanoparticles for targeted phototherapy and cancer imaging
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DOI：
10.1088/0957-4484/21/10/105105
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发表时间：
2010-03-12
期刊：
影响因子：
3.5
通讯作者：
Batt, Carl A.
中科院分区：
文献类型：
--
作者：
Kirui, Dickson K.;Rey, Diego A.;Batt, Carl A.
通过热分解技术合成的金和氧化铁混合纳米颗粒（HNP）用单链抗体scFv生物功能化，所述单链抗体结合结肠直肠癌细胞上存在的A33抗原。HNP-scFv缀合物在水溶液中是稳定的，具有44 emu g（-1）的磁化强度值，并且在800 nm处表现出强的吸光度。在这里，我们测试这种材料在靶向，成像和选择性热杀死结直肠癌细胞。细胞摄取研究显示，表达A33的细胞以比不表达A33抗原的细胞高5倍的速率摄取A33 scFv缀合的HNP。激光照射研究表明，在使用808 nm连续波激光二极管以5.1 W cm（-2）进行6分钟激光处理后，暴露于靶向HNP的约53%的A33表达细胞被杀死，而< 5%的A33非表达细胞被杀死。在较高的强度下，31.5 W cm（-2），暴露6分钟后，A33表达细胞和A33非表达细胞的热破坏分别增加到99%和40%。对激光照射的A33抗原表达细胞的流式细胞术分析显示，在5.1 W cm（-2）下，坏死相关的细胞死亡是细胞死亡的主要模式，在更高的激光功率下，坏死相关的细胞死亡增加。这些结果表明，这种新型的生物共轭混合纳米粒子可以作为一种有效的抗原靶向光热治疗剂，用于癌症治疗以及磁共振成像的探针。
Gold and iron oxide hybrid nanoparticles (HNPs) synthesized by the thermal decomposition technique are bio-functionalized with a single chain antibody, scFv, that binds to the A33 antigen present on colorectal cancer cells. The HNP-scFv conjugates are stable in aqueous solution with a magnetization value of 44 emu g(-1) and exhibit strong optical absorbance at 800 nm. Here we test this material in targeting, imaging and selective thermal killing of colorectal cancer cells. Cellular uptake studies showed that A33-expressing cells take up the A33scFv-conjugated HNPs at a rate five times higher than cells that do not express the A33 antigen. Laser irradiation studies showed that approximately 53% of the A33-expressing cells exposed to targeted HNPs are killed after a six-minute laser treatment at 5.1 W cm(-2) using a 808 nm continuous wave laser diode while < 5% of A33-nonexpressing cells are killed. At a higher intensity, 31.5 W cm(-2), the thermal destruction increases to 99 and 40% for A33-expressing cells and A33 nonexpressing cells, respectively, after 6 min exposure. Flow cytometric analyses of the laser-irradiated A33 antigen-expressing cells show apoptosis-related cell death to be the primary mode of cell death at 5.1 W cm(-2), with increasing necrosis-related cell death at higher laser power. These results suggest that this new class of bio-conjugated hybrid nanoparticles can potentially serve as an effective antigen-targeted photothermal therapeutic agent for cancer treatment as well as a probe for magnetic resonance-based imaging.