新型光敏剂DVDMS声、光活性分析及抗肿瘤机制研究

新型光敏剂-华卟啉钠（DVDMS）的光、声活性均优于目前国内外应用的光敏剂，初步研究表明DVDMS不仅能显著提高PDT抗癌效应，同时兼有SDT抑制肿瘤细胞增殖作用，尤其在声光联合疗法（SPDT）新探索中表现出更好的抗癌潜质。本项目拟选取多种不同组织来源的肿瘤细胞和荷瘤鼠为实验模型，筛选优化不同的理化参数组合，研究DVDMS所介导的声光联合疗法（DVDMS-SPDT）抗肿瘤效应的有效性、靶向性、广谱性和细胞敏感性；分析DVDMS作用的胞内靶点，药代动力学变化规律及声光参数变化与DVDMS在肿瘤细胞内的协同作用；从离体和在体两个侧面研究SPDT作用于肿瘤组织/细胞后形态结构、生理功能及相关蛋白表达与活性变化，分析DVDMS-SPDT诱导肿瘤细胞凋亡及其伴行的细胞自噬功能转换，阐明杀伤不同肿瘤细胞的路径、死亡模式，相关的细胞信号通路和基因调控，揭示DVDMS-SPDT抗肿瘤的细胞分子生物学机制。

A novel photosensitizer, Sinoporphyrin sodium (DVDMS), has been proven to have better response in either photodynamic therapy or sonodynamic therapy when comparing to any other general photosensitizers used worldwide. Our preliminary data indicate that DVDMS mediated Sono-Photodynamic therapy (SPDT) enjoys an added advantage than any monotherapy. In order to identify the anti-tumor effects and applicability of DVDMS-SPDT, tumor models from various tissues and their corresponding tumor-bearing mice will be used in this project. At first, we will determine the cellular targets of DVDMS, its pharmacokinetic varying pattern and the synergetic sono-/photo- parameter settings in cancer treatment. We then analysis the general anti-tumor effects of DVDMS-SPDT in distinct malignant cells, and the more sensitive cell lines will be chosen for further studies. Prior to/after DVDMS-SPDT treatment, the microstructural and ultrastructural changes, the physiological function changes and the properties of key biomacromolecules will be measured from in vivo and in vitro. Combining with molecular methods, we will further investigate the related cell signaling and gene regulation involved in DVDMS-SPDT induced cellular apoptotic and autophagic responses. Taken together, the studies on the cellular and molecular mechanisms involved in the anti-tumor effects of DVDMS-SPDT will finally allow us to lay a theoretical and experimental foundation for the clinical use of such a promising therapy.