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用于癌症光化疗联合治疗的多功能杂化材料。

Multifunctional hybrid materials for combined photo and chemotherapy of cancer.

机构信息

Instituto de Tecnología Química (UPV-CSIC), Avda. Los Naranjos s/n, 46022 Valencia, Spain.

出版信息

Dalton Trans. 2012 Aug 21;41(31):9286-96. doi: 10.1039/c2dt30381g. Epub 2012 May 4.

DOI:10.1039/c2dt30381g
PMID:22555652
Abstract

Combined chemo and photothermal therapy in in vitro testing has been achieved by means of multifunctional nanoparticles formed by plasmonic gold nanoclusters with a protecting shell of porous silica that contains an antitumor drug. We propose a therapeutic nanoplatform that associates the optical activity of small gold nanoparticles aggregates with the cytotoxic activity of 20(S)-camptothecin simultaneously released for the efficient destruction of cancer cells. For this purpose, a method was used for the controlled assembly of gold nanoparticles into stable clusters with a tailored absorption cross-section in the vis/NIR spectrum, which involves aggregation in alkaline medium of 15 nm diameter gold colloids protected with a thin silica layer. Clusters were further encapsulated in an ordered homogeneous mesoporous silica coating that provides biocompatibility and stability in physiological fluids. After internalization in 42-MG-BA human glioma cells, these protected gold nanoclusters were able to produce effective photothermolysis under femtosecond pulse laser irradiation of 790 nm. Cell death occurred by combination of a thermal mechanism and mechanical disruption of the membrane cell due to induced generation of micrometer-scale bubbles by vaporizing the water inside the channels of the mesoporous silica coating. Moreover, the incorporation of 20(S)-camptothecin within the pores of the external shell, which was released during the process, provoked significant cell death increase. This therapeutic model could be of interest for application in the treatment and suppression of non-solid tumors.

摘要

通过具有多孔硅壳的等离子体金纳米簇形成多功能纳米粒子,已经在体外测试中实现了联合化疗和光热疗法,该多孔硅壳中含有抗肿瘤药物。我们提出了一种治疗性纳米平台,将小金纳米颗粒聚集体的光学活性与同时释放的 20(S)-喜树碱的细胞毒性活性相结合,从而有效地破坏癌细胞。为此,我们使用一种方法将金纳米粒子在碱性介质中进行可控组装成具有定制吸收截面的稳定聚集体,该方法涉及用薄的二氧化硅层保护的 15nm 直径金胶体在碱性介质中的聚集。然后将聚集体进一步封装在有序的均匀介孔硅涂层中,该介孔硅涂层提供了生物相容性和在生理流体中的稳定性。在 42-MG-BA 人神经胶质瘤细胞内化后,这些受保护的金纳米簇能够在 790nm 的飞秒脉冲激光照射下产生有效的光热解。细胞死亡是通过热机制和由于介孔硅涂层通道内的水蒸发而导致的细胞膜的机械破坏的组合而发生的,同时诱导产生微米级的气泡。此外,在外部壳的孔内掺入 20(S)-喜树碱,其在该过程中释放,引起了显著的细胞死亡增加。这种治疗模型可能对非实体瘤的治疗和抑制有应用价值。

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