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新型智能金纳米粒子用于乳腺癌细胞的化学光热消融的简单策略。

A simple strategy for chemo-photothermal ablation of breast cancer cells by novel smart gold nanoparticles.

机构信息

Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Photodiagnosis Photodyn Ther. 2019 Dec;28:25-37. doi: 10.1016/j.pdpdt.2019.08.019. Epub 2019 Aug 24.

DOI:10.1016/j.pdpdt.2019.08.019
PMID:31454714
Abstract

Combined therapeutics dependent on the synergistic effect between photothermal therapy (PTT) and chemotherapy have been anticipated to be the next generation of cancer treatment. For this purpose, a novel gold hydrosol was synthesized by a one-pot approach using poly (2-(dimethylamino) ethyl methacrylate-co- N-isopropylacrylamide-co- 2-vinylpyridine) P(DMAEMA-co-NIPAAM-co-VP) terpolymers as a reducing and stabilizing agent. The synthesized gold hydrosol was recoated by a novel carboxylic acid rich poly (N-isopropyl acrylamide-co-maleic anhydride-graft-citric acid) (PNIPAAm-co-PMA-g-CA) copolymer. Then the gold nanoparticles conjugated with Doxorubicin (DOX) and served as a smart photo synthesizer for chemo/photothermal therapy of MCF-7 breast cancer cells. The synthesized nanoparticles had mono-dispersed spherical morphology with a diameter below 30 nm. Our results from cellular uptake indicated that around 100% of the particles were uptake by MCF-7 cells in the first 3 h of exposure time. The temperature of nanocomposites considerably went up to 45 °C with 10 min exposure to near-infrared irradiation. As a striking result, a single round of PTT combined with a sub-therapeutic dose of DOX revealed a synergistic effect with an ability of robust anti-tumor response up to 99.99% (sum of the population of apoptotic and necrotic cells) demonstrated by Annexin-V, cell cycle and DAPI staining techniques. In conclusion, Near-infrared-mediated photothermal conversion exhibited high effectiveness of a combinational chemo-thermotherapy to treat cancer cells.

摘要

联合治疗依赖于光热治疗(PTT)和化学疗法的协同作用,被认为是下一代癌症治疗方法。为此,采用一锅法合成了一种新型金纳米水溶胶,使用聚(2-(二甲氨基)乙基甲基丙烯酸酯-co-N-异丙基丙烯酰胺-co-2-乙烯基吡啶)P(DMAEMA-co-NIPAAM-co-VP)三共聚物作为还原剂和稳定剂。合成的金纳米水溶胶被新型富羧酸的聚(N-异丙基丙烯酰胺-co-马来酸酐-接枝-柠檬酸)(PNIPAAm-co-PMA-g-CA)共聚物重新包覆。然后将金纳米粒子与阿霉素(DOX)缀合,并作为 MCF-7 乳腺癌细胞化学/光热治疗的智能光合成器。合成的纳米粒子具有单分散的球形形态,直径小于 30nm。我们的细胞摄取结果表明,在暴露时间的前 3 小时内,约 100%的颗粒被 MCF-7 细胞摄取。纳米复合材料的温度在 10 分钟近红外辐射照射下可显著升高至 45°C。令人瞩目的是,单次 PTT 联合亚治疗剂量 DOX 显示出协同作用,通过 Annexin-V、细胞周期和 DAPI 染色技术,具有高达 99.99%(凋亡和坏死细胞群体之和)的强大抗肿瘤反应能力。总之,近红外介导的光热转换在联合化学-热疗治疗癌细胞方面表现出很高的有效性。

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