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金杂化纳米颗粒用于靶向光疗和癌症成像。

Gold hybrid nanoparticles for targeted phototherapy and cancer imaging.

机构信息

Graduate Field of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

出版信息

Nanotechnology. 2010 Mar 12;21(10):105105. doi: 10.1088/0957-4484/21/10/105105. Epub 2010 Feb 15.

Abstract

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.

摘要

金铁氧化物杂化纳米粒子(HNPs)通过热分解技术合成,并用单链抗体 scFv 进行生物功能化,该抗体与结直肠癌细胞上的 A33 抗原结合。HNPs-scFv 缀合物在水溶液中稳定,磁化值为 44 emu g(-1),在 800nm 处表现出强吸光度。在这里,我们将这种材料用于结直肠癌细胞的靶向、成像和选择性热杀伤。细胞摄取研究表明,表达 A33 的细胞摄取 A33scFv 缀合的 HNPs 的速度比不表达 A33 抗原的细胞高五倍。激光辐照研究表明,在用 808nm 连续波激光二极管在 5.1 W cm(-2) 的激光照射 6 分钟后,暴露于靶向 HNPs 的约 53%的表达 A33 的细胞被杀死,而 < 5%的不表达 A33 的细胞被杀死。在更高的强度下,31.5 W cm(-2),暴露 6 分钟后,表达 A33 的细胞和不表达 A33 的细胞的热破坏分别增加到 99%和 40%。激光照射的表达 A33 抗原的细胞的流式细胞术分析表明,在 5.1 W cm(-2) 时,细胞死亡的主要模式是与凋亡相关的细胞死亡,随着激光功率的增加,与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杂化纳米粒子有可能作为一种有效的抗原靶向光热治疗剂用于癌症治疗,以及一种基于磁共振成像的探针。

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