三展示噬菌体-纳米系统应用于白色念珠菌感染富集性检测和靶向治疗的研究

A variety of fungi showed different sensitivity on antifungal agents. Systemic Candida albicans infection is a life treating disease in hospitalized patients. No sensitivity detection and treatment methods is resulting in significant mortality. So it is a necessary to increase markers concentration and develop targeted drug. Magnetic nanoparticle could be enriched under the magnetic field, and our study indicated that phage–magnetic nanocomposites could specifically enrich the detected material. The project is on the basis of triple displayed phage, intends to use phage display technology and nanotechnology to develop research of candida albicans diagnosis and treatment. There are two works: (1) Construction of triple displayed phage, phage–magnetic nanocomposites simultaneously displayed VKYTS peptide and LKVIRK peptide are use to enrich anti-Hsp90 and anti-Sap2 antibodies, and detected candidiasis in cancer pateints; (2) Phage simultaneously displayed the targeting peptide to C. albicans and drug sustained peptide are used to research immunotherapy to candidiasis in Candida albicans infection animal. The triple displayed phage was employed as a novel capture probe to develop a new ELISA method, which was significantly improved the detection rate, the phage-nanocomposites emerged as powerful agents to confer sensitive detection and trageted theraphy against clinical infections, which has potential to be widely used in the life sciences, clinical medicine, and environmental sciences.

白色念珠菌易产生耐药性，系统性感染缺乏有效的早期诊断方式，死亡率高。增加诊断物的浓度、实施抗耐药性的靶向治疗是提高系统性真菌感染诊治效力的关键。磁性纳米颗粒在磁场作用下定向富集，展示外源多肽的噬菌体具有特异性，我们研究表明噬菌体纳米材料兼具二者的特性，适用于低浓度物质的富集和靶向治疗的研究。为了尽早实施抗真菌治疗，本项目基于三展示噬菌体载体，以早期诊断标志物Sap2和耐药性蛋白Hsp90为靶点，利用噬菌体展示、纳米生物学等技术，进行噬菌体-纳米系统应用于白色念珠菌感染检测和治疗的研究：1.制备噬菌体磁性纳米材料，研究其对低浓度物质的联合富集作用，对易感人群进行白色念珠菌感染的预测；2.制备噬菌体生物纳米材料，研究其靶向和抗耐药作用，对感染动物模型进行抗真菌治疗。本研究将指导真菌感染的用药方案，拓展应用于环境、食品等领域低浓度物质的检测；为降低真菌耐药性、靶向治疗提供新的研究思路。

白色念珠菌易产生耐药性，系统性感染缺乏有效的早期诊断方式，死亡率高。增加诊断物的浓度、实施靶向治疗是提高系统性真菌感染诊治效力的关键。磁性纳米颗粒在磁场作用下定向富集，展示外源多肽的噬菌体具有特异性，我们研究表明噬菌体纳米材料兼具二者的特性，适用于低浓度物质的富集和靶向治疗的研究。为了尽早实施抗真菌治疗，本项目基于多展示噬菌体载体，以早期诊断标志物Sap2和耐药性蛋白Hsp90为靶点，利用噬菌体展示、 纳米生物学等技术，进行噬菌体-纳米系统应用于白色念珠菌感染检测和治疗的研究：1.成功制备了噬菌体磁性纳米材料，利用其对Sap2抗体和Hsp90抗体的富集作用，对易感人群进行白色念珠菌感染的抗体检测，研究发现利用噬菌体纳米材料进行抗体检测显著提高检测的灵敏性；2.成功制备噬菌体生物纳米材料，对白色念珠菌感染动物模型进行抗真菌治疗，研究表明噬菌体生物纳米材料可以靶向白色念珠菌，显著提高感染动物模型的存活率。本研究可以指导真菌感染的用药方案，拓展应用于环境、食品等领域低浓度物质的检测，为降低真菌耐药性、靶向治疗提供新的研究思路。