基于近红外发光长余辉材料的多功能纳米探针的构建及多模态成像和治疗应用

The molecular probe based on the near-infrared (NIR) emitting persistent luminescent nanoparticles (PLNPs) have great applied valve and potential for disease early detection and therapy with the advantages of no need for in situ excitation, the absence of background noise, high signal-to-noise ratio, and deep tissue penetration. However，some problems, including large grain size, irregular shape of particles，and short afterglow time severely restricted the wide application of PLNPs in the biomedical area. Here, we aim to develop Cr3+ doped gallate PLNPs with small grain size, controllable shape by a mesoporous silica template method. The co-doping of rare earth ion will improve the NIR afterglow time and photo-stimulate luminescence of PLNPs. The multifunctional targeting probe with high sensitivity, high resolution, high signal-to-noise ratio and low background noise will fabricate via the surface modification of PLNPs with PEG, folic acid and magnetic nanoparticles Fe3O4. The multifunctional nanoprobe will apply to in vivo optical/magnetic resonance imaging and photothermal therapy for tumor, and will achieve diagnosis of disease with simultaneous therapy. This project will promote the disease early diagnosis and treatment, evaluation of therapy and drug development.

基于近红外发光长余辉纳米粒子的分子探针具有免原位激发，无背景干扰、高信噪比、较深的组织穿透性等优点，在疾病早期诊断和治疗方面具有重要应用价值和发展潜能。然而颗粒尺寸大、形貌不规则、余辉时间短等问题目前严重制约长余辉纳米粒子在生物医学领域中广泛应用。本项目拟以介孔二氧化硅为模板，制备尺寸小、形貌可控的Cr3+掺杂镓酸盐长余辉纳米粒子。通过稀土离子共掺杂，提高长余辉纳米粒子的近红外余辉时间和光激励发光性能。长余辉纳米粒子表面进一步与聚合物PEG、靶标分子叶酸和磁性纳米粒子Fe3O4功能化，构建高灵敏、高分辨率、高信噪比、低背景干扰的靶向探针，并应用于活体肿瘤的光学/磁共振成像和光热治疗研究，实现诊断和治疗一体化。本项目对于促进疾病早期诊断和治疗、疗效监测和药物研发等方面具有重要意义。

本项目以Cr3+共掺杂镓酸盐长余辉体系为主，发展了一系列尺寸小、形貌可控、近红外（NIR）余辉时间长的长余辉发光纳米颗粒（PLNPs）的制备方法。通过表面功能化，构建了基于PLNPs的光学/磁共振成像多模态探针，并应用于多模态成像和光热治疗。为制备新型PLNPs及其应用提供了新方法。公开发表了学术论文5篇，申请国家发明专利3项。