RGD肽修饰量子点在胰腺癌光动力治疗中的作用及机制研究

Photodynamic Therapy（PDT) possesses potential advantages in pancreatic cancer. In our previous experiments, we have successfully synthesized RGD modified quantum dots(QDs) as a new type of photosensitizer. The photodynamic therapy with QDs-RGD as photosensitizer significantly inhibited cell proliferation. The FCM revealed PDT group had more significant cell apoptosis rate compared to control cells. The expression of Mcl-1 and Akt mRNA were down-regulated, while expression of TRAIL mRNA was up-regulated after pancreatic cancer cells treated with PDT. Therefore, our hypothesis is QDs-RGD injected into the tumor directly could be a new type of photosensitizer of PDT in pancreatic cancer. Our study is aimed to detcect the efficiency of QDs-RGD mediated PDT in xenografted pancreatic cancer, while the safty is evaluated through observing the distribution of QDs-RGD in the animal. The localization of QDs-RGD should be investigated in the pancreatic cancer cells by electron microscope and fluorescent microscope. We want to screen the relitive molecules by protein microarray, and we will investigate the effects of the candidates in vitro and in vivo. The aim is to provide new ideas and experimental basis for PDT of advanced pancreatic cancer with EUS.

光动力疗法（PDT）是一种有发展前景的进展期胰腺癌治疗方案。前期实验中，已成功合成RGD修饰的量子点作为新型光敏剂；体外实验提示量子点-RGD介导的光动力可抑制胰腺癌细胞SW1990的增殖，同时促进其凋亡；量子点-RGD介导的PDT可抑制增殖基因Akt及抑制凋亡基因Mcl-1 的表达，而上调凋亡诱导配体TRAIL的表达。因此，我们认为量子点-RGD可以作为一种新型光敏剂通过瘤内注射法进行胰腺癌的PDT。本研究旨在进一步通过胰腺癌移植瘤动物模型证实此种方法的有效性；并对量子点-RGD在体内分布情况进行检测从而评估其安全性；通过电镜及荧光显微镜观察量子点-RGD在胰腺癌细胞内的分布及PDT后亚细胞结构的变化；通过蛋白芯片筛选出量子点-RGD介导的PDT的相关分子；并通过体内、体外实验进一步证实筛选出分子的作用。我们的课题为超声胃镜引导下的光动力治疗胰腺癌提供了新思路和实验基础。

光动力疗法（PDT）是一种有发展前景的进展期胰腺癌治疗方案。前期实验中，.已成功合成 RGD 修饰的量子点作为新型光敏剂；体外实验提示量子点-RGD 介导的光动力作用可抑制胰腺癌细胞 SW1990 的增殖，同时促进其凋亡。因此，我们认为量子点-RGD 可以作为一种新型光敏剂通过瘤内注射法进行胰腺癌的 PDT。本研究探究了胰腺癌移植瘤动物模型中量子点-RGD的体内分布、给药方式、毒性、安全性及生长抑制作用；体外研究观察量子点-RGD 在胰腺癌细胞内的分布、PDT后亚细胞结构的变化、侵袭能力的改变及杀伤机制；通过蛋白芯片筛选出量子点-RGD 介导的 PDT 的可能分子及相关通路。我们研究结果显示：量子点-RGD可有效抑制胰腺肿瘤细胞的生长，且毒性较小；然而可能造成PDT后残存的胰腺癌细胞侵袭能力增强，故而联合用药是未来的研究方向。我们的研究证明了量子点-RGD是一种高效、安全的可用于胰腺癌治疗的新型光敏剂，为超声胃镜引导下的光动力治疗胰腺癌提供了实验基础。