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蛋白纳米反应器辅助的半导体纳米晶合成及其在肿瘤诊疗中的应用
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摘要
本文研究了一种用于肿瘤多模态成像和光热治疗的新型多功能半导体硫族化合物蛋白纳米粒。采用具有临床应用前景的蛋白质(如白蛋白)作为纳米反应器,利用蛋白质的仿生合成原理,将过渡金属离子(如Cu~(~(2+))、Co~(2+)、Ni~(2+)等)与蛋白的氨基酸残基通过静电相互作用形成成核中心,并通过其与硫离子的沉淀反应,诱导过渡金属硫化物纳米晶在蛋白纳米反应器中的成核与可控生长,合成出具有近红外吸收和光热效应的过渡金属硫化物蛋白纳米粒,有效实现了肿瘤的光热消融治疗。在此基础上,进一步在蛋白纳米粒表面偶联荧光染料、核素等,可赋予纳米粒的多模态肿瘤成像(如荧光、光声、SPECT/CT等)能力,实现肿瘤的诊疗一体化。本研究为半导体蛋白纳米粒在肿瘤成像、靶向治疗中的应用提供了良好的基础。
We report a proof-of-concept controllable synthesis of stoichiometric transition metal sulfide nanocrystals using the expansive protein nanoreactors with facile functionalization for multimodal imaging and efficient photothermal tumor ablation. Various transition metal(Co, Ni, and Cu) sulfide nanocrystals with remarkable NIR absorbance and ultrahigh photothermal conversion efficiency are synthesized using the protein nanoreactors in a controlled manner, which are further functionalized with the imaging agents including NIR fluorescence dye(Cy7.5) and radionuclide(~(99m)Tc) through the facile coupling. As a consequence, the nanocrystals generate the complementary imaging modalities including near-infrared fluorescence(NIRF), photoacoustics(PA), and single-photon emission computed tomography/computed tomography(SPECT/CT) for precise tumor localization. Meanwhile, the nanocrystals also exhibit potent hyperthermia upon irradiation, which leads to effective tumor ablation. Our proof-of-concept design of protein nanoreactors represents a general and versatile platform for rationally designed multimodal imaging and therapeutic applications.
引文
[1]Wang Y,Yang T,Ke HT,et al.Adv Mater.2015;27:3874.
    [2]Yang T,Wang Y,Ke HT,et al.Adv Mater,2016,DOI:10.1002/adma.201506119

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