基于上转换纳米颗粒和重组蛋白的发光治疗纳米复合物的合成

D. Bausheva, N. Shilyagina, V. Vodeneev, S. Deev, A. Zvyagin, E. Guryev
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摘要

治疗学是一个快速发展的生物医学领域,其目标是开发兼具诊断和治疗功能的多功能药物。这项工作描述了基于上转换纳米颗粒和双功能蛋白的her2特异性治疗纳米复合物的生产。采用NaY0.794Yb0.2Tm0.006F4/NaYF4核壳结构的无机纳米晶体作为多功能配合物的组装平台。研究表明,上转换纳米颗粒(UCNP)在可见光和红外光谱区域具有明显的最大光致发光发射,可通过光学成像方法有效地在体内成像细胞和组织。用额外的外壳覆盖UCNP可以实现它们的胶体稳定性,并附加额外的外部模块。重组靶向毒素DARPin-LoPE对表达HER2受体的肿瘤细胞具有特异性毒性,被用作纳米复合物的治疗模块。由于其组成中包含DARPin引导模块,治疗复合物naff -DARPin- lope被证明能够选择性地结合高表达HER2受体的肿瘤细胞。
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SYNTHESIS OF LUMINESCENT THERANOSTIC NANOCOMPLEXES BASED ON UPCOVERSION NANOPARTICLES AND RECOMBINANT PROTEINS
Theranostics is a rapidly developing field of biomedicine, aimed at the development of multifunctional agents with diagnostic and therapeutic properties simultaneously. This work describes the production of HER2-specific theranostic nanocomplexes based on upconversion nanoparticles and bifunctional proteins. Inorganic nanocrystals of the NaY0.794Yb0.2Tm0.006F4/NaYF4 core/shell structure were used as a platform for the assembly of the multifunctional complex. Upconversion nanoparticles (UCNP) were shown to have pronounced maxima of photoluminescence emission in the visible and infrared regions of the spectrum, which provides effective in vivo imaging of cells and tissues by optical imaging methods. Covering UCNP with additional shells allows achieving their colloidal stability and attaching additional external modules to them. The recombinant targeting toxin DARPin-LoPE, which has specific toxicity against tumor cells expressing the HER2 receptor, was used as a therapeutic module of the nanocomplexes. The theranostic complex NAF-DARPin-LoPE was shown to be able to selectively bind to tumor cells hyperexpressing the HER2 receptor due to the DARPin guide module included in its composition.
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