X-射线激发多孔硅复合纳米粒用于肝癌的光动力学治疗

Photodynamic therapy (PDT), as a minimally invasive treatment for tumour, is highly favored in clinical applications in recent years. However, the photo toxicity of traditional photosensitizers and their inapplicability to deep cancer become a big problem that limits the extensive use of PDT.Here, our objective is to prepare a kind of biocompatible nanocomposite for photodynamic therapy to deep tissue, covering the shortage of traditional photosensitizers. Porous silicon nanoparticles (pSi), which can generate singlet oxygen, are prepared by electrochemical etching of single-crystal silicon wafers in ethanolic HF solution. Magnetic nanoparticles and X-ray-activable nanoscintillators are assembled into the inner-pores of pSi to construct a composite nanodevice. The behavior of as-constructed nanodevice to generate singlet oxygen under the stimulation of X-ray is investigated. After conjugated with targeted molecules, these nanodevices are exploited for magnetic resonance imaging and photodynamic therapy to hepatocellular carcinoma. This project provides a new and safe way for photodynamic therapy to deep tissue cancer, meanwhile, some scientific problems invoved are deeply investigated. It is of great academic significance and clinical value.

光动力学疗法作为一种微创性的肿瘤治疗手段，近几年来倍受青睐。然而，传统光敏剂的光毒性以及无法适用于深部组织肿瘤光动力学治疗成为限制其广泛应用的最大因素。本项目旨在基于前期工作基础上研究一种生物相容性好、可用于深部组织光动力学治疗的复合纳米粒，以改善传统光敏剂的不足。采用电化学刻蚀方法制备能产生单线态氧的多孔硅纳米粒子，并利用其多孔结构将磁性纳米颗粒和可被X-射线激发产生荧光的纳米闪烁晶体组装到其内部孔径中，构建一种复合纳米器件，进行表面修饰和靶向分子偶联后，研究其在X-射线激发下通过能量转移产生单线态氧的行为，考察其对体外肝癌细胞/原位肝癌的磁共振成像和光动力学治疗效果。本项目为深部组织肿瘤的光动力学治疗提供了一条崭新的、安全的途径，并对相关科学问题进行深入探讨，具有重要的学术意义和临床价值。

光动力学疗法作为一种微创性的肿瘤治疗手段，近几年来倍受青睐。然而，传统光敏剂的光毒性以及无法适用于深部组织肿瘤光动力学治疗成为限制其广泛应用的最大因素。采用水热法制备了具有多孔结构的LaF3:Tb纳米闪烁晶体，该纳米颗粒具有较强的X射线阻挡能力，且在X射线的激发下具有较强的荧光。我们利用该纳米闪烁晶体作为光敏剂（玫瑰红）的载体，构建荧光共振能量转移体系。由于纳米闪烁晶体荧光发射光谱与玫瑰红吸收光谱较大程度的匹配，二者之间的荧光共振能量转移效率可以达到85%以上。并且，该纳米复合体系在外部激发下能通过FRET过程产生大量的单线态氧。进一步，我们采用Stober法在LaF3:Tb纳米闪烁晶体表面修饰一层二氧化硅，修饰以后的纳米粒具有较高的胶体稳定性和较好的生物相容性，通过共价偶联将玫瑰红负载到纳米粒表面，构建得到的复合纳米材料也能通过FRET效应在外部激发下产生单线态氧。本项目为深部组织肿瘤的光动力学治疗提供了一条崭新的、安全的途径，并对相关科学问题进行深入探讨，具有重要的学术意义和临床价值。