Nd3+敏化上转换纳米晶与介孔二氧化硅及贵金属纳米复合药物载体在癌症诊疗中的应用研究

Cancer is one of the most common causes of death in the world. up-conversion nano-particles (UCNPs) functionalized with mesoporous silica composites have been prove to be good drug carriers, which could combine diagnosis with therapy of cancer. However, their applications have been strongly limited because of the low luminescent efficiency of UCNPs. Nd3+-sensitized core-shell structured UCNPs can effectively enhance the UC luminescence and solve this problem. Moreover, through further compositing with noble metal nanoparticles, which have excellent photothermal effect, the drug therapy effect could be highly enhanced. In this project, a kind of multifunctional nano-composites will be designed and prepared as drug carrier, which combining several advantages of Nd3+-sensitized up-conversion luminescence, mesoporous channels, plasma enhancement, and photo-thermal responses into one single entity. The as-prepared nano-composites were further modified using different surfactant and biological conjugated with different molecular to gain water solubility and nuclear targeting properties. Upon NIR irradiation, the noble metal nanoparticals can convert the absorbed light into heat, and promotes the destruction of biological samples. Futhermore, the drug release can also be promoted on the same time due to the photothermal effect. Such novel multifunctional anticancer drug delivery systems, which possess the bio-imaging effect, and combine hyperthermia with the chemotherapeutic drugs by synergistic effect, should be of high potential in cancer theranostics.

上转换纳米晶与介孔二氧化硅的复合物是一种优秀的药物载体，然而其发展和应用却受到上转换纳米晶荧光效率较低的问题的限制，Nd3+敏化核壳结构上转换纳米晶具有优异的荧光性能，可有效的解决这一问题，且十分适合与贵金属纳米颗粒复合形成光热药物体系，通过光热作用对药物治疗的效果进行增强。本项目中，我们将利用Nd3+敏化上转换纳米晶与介孔二氧化硅和贵金属纳米晶同时复合，并对材料进行靶向修饰，制备一类新型的多功能纳米药物载体材料。贵金属纳米晶的光热转换性能不仅能够对癌细胞产生治疗作用，还将促进化学药物在病灶处的释放，形成双重的治疗效果。Nd3+敏化的核壳结构的上转换纳米晶可以在实现上转换荧光增强的基础上，丰富荧光材料的激发手段，为贵金属热敏剂的选择及充分利用提供有利条件。该类同时具有生物成像和光热-化学协同治疗效果的多功能复合纳米药物载体材料，在癌症诊疗领域具有重要的研究价值和巨大的应用潜力。

稀土发光材料由于具有物理化学性质稳定、发射谱狭窄、光色纯度高、发射波段宽、Stokes位移大、荧光寿命长等优点，在生物标记、生物成像方面具有潜在的应用前景。基于分子影像的个性化医疗将成为未来医学的发展方向。上转换纳米晶与介孔二氧化硅的复合物是一种优秀的药物载体，在多功能癌症诊疗领域有很好的应用前景。本项目拟系统研究稀土上转换荧光纳米晶复合物在深组织生物成像领域的应用及光热治疗、光动力治疗领域的应用。已报道的该类纳米晶存在荧光效率低和组织透深浅等不足，且纳米晶的安全性研究刚刚起步，分析结果多有矛盾。针对以上问题，本项目首先利用软化学法制备多种稀土上转换荧光纳米晶，如核壳结构NaGdF4:Yb/Tm@NaGdF4:Yb@NaNdF4:Yb@NaGdF4；然后，通过调整纳米晶的组成、尺寸和结构等因素增强材料的荧光强度开发和优化纳米晶的亲水修饰方法，解决修饰后纳米晶发光强度低的关键问题。发现调整材料组成、结构和表面性质能消除荧光猝灭影响，构筑核壳结构、掺杂优化和基质调变等方法可将发光强度提高20~200倍，同时，揭示了上转换发光的能量传递机制。开展了稀土发光纳米材料的多模式生物成像研究，发现利用多功能稀土材料的不同组分能够实现单一粒子的多模式成像，据此提出利用多功能稀土材料实现单一粒子的高效上转换发光、核磁成像性质，并揭示了其在诊断和荧光监控领域应用的可行性。将贵金属金及金氧化物与稀土纳米粒子复合，通过近红外光敏化及粒子间的能量传递，实现了近红外光响应下的溶解氧释放，增强了光动力治疗效果。将稀土发光纳米材料用于红外光诱发的多模式光学治疗载体，揭示了单一多功能纳米粒子的多模式光学治疗性质。此外，项目还开发了两种应用于细胞成像的聚合诱导发光体，并将探索其与稀土发光纳米粒子的结合应用，以期待获得更好的癌症诊疗效果。