量子点-RGD探针光动力疗法联合吉西他滨治疗胰腺癌荷瘤裸鼠初探

背景:胰腺癌发病隐匿,进展迅速,预后极差。光动力疗法(PDT)是20世纪80年代发展起来的一种新型抗肿瘤治疗手段。目前关于PDT在体内靶向治疗胰腺癌的研究甚少。目的:探讨以量子点-RGD(QDs-RGD)探针为光敏剂的PDT联合吉西他滨对胰腺癌移植瘤裸鼠的治疗效应。方法:合成QDs-RGD探针,制备胰腺癌移植瘤裸鼠模型。采用小动物活体成像术观察QDs-RGD、QDs探针注射入模型裸鼠体内1、5、10、24 h后的显影情况。取40只造模成功的裸鼠,随机分为5组:对照组(不给予任何治疗);单纯光照组(激光630 nm,120 J/cm2,持续照射20 min);PDT组(QDs-RGD 0.5 nmol+激光照射);吉西他滨组(吉西他滨50 mg/kg);联合治疗组(QDs-RGD 0.5 nmol+激光照射+吉西他滨50 mg/kg)。第18 d处死全部裸鼠,取出瘤体,称重并测量体积,计算抑瘤率。结果:QDs-RGD注射1 h后,肿瘤显影逐渐清晰,注射5 h后显影达高峰,随后逐渐减弱。QDs于瘤体附近的聚集浓度明显低于QDs-RGD,注射10 h后肿瘤部位已无显影。PDT组、吉西他滨组和联合治疗组的瘤重、瘤体积均显著低于对照组和单纯光照组(P0.01),其中联合治疗组又显著低于PDT组和吉西他滨组(P0.05);对照组与单纯光照组间、PDT组与吉西他滨组间瘤重、瘤体积差异均无统计学意义(P0.05)。联合治疗组、吉西他滨组、PDT组的抑瘤率分别为70.5%、43.5%、37.1%。结论:以QDs-RGD探针为光敏剂的PDT联合吉西他滨能明显抑制裸鼠体内胰腺癌移植瘤的生长,为临床治疗胰腺癌提供了一条新思路。

Efficacy of Quantum Dots-RGD Based Photodynamic Therapy Combined with Gemcitabine for Treatment of Pancreatic Cancer Xenograft in Nude Mice

Background：Pancreatic cancer is obscure in onset and progresses rapidly with very poor prognosis. Photodynamic therapy（ PDT）has been developed as a novel anti-tumor treatment modality since 1980s. At present,there are only limited researches on pancreatic cancer treated with PDT in vivo. Aims：To investigate the efficacy of quantum dots-RGD （ QDs-RGD）based PDT combined with gemcitabine for treatment of pancreatic cancer xenograft in nude mice. Methods：QDs-RGD probe was synthesized and nude mice bearing pancreatic cancer xenograft was established. Nude mice were imaged at 1,5,10 and 24 hours after injection of QDs-RGD and QDs by in vivo imaging system. Forty model nude mice were randomly divided into five groups：control group（ without any treatment）,simple illumination group（ laser 630 nm, 120 J/cm2,20 min）,PDT group（QDs-RGD 0. 5 nmol＋laser irradiation）,gemcitabine group（gemcitabine 50 mg/kg）and combination group（QDs-RGD 0. 5 nmol＋laser irradiation＋gemcitabine 50 mg/kg）. All the nude mice were sacrificed 18 days later. Tumor weight and volume were measured and tumor inhibition rate was calculated. Results：Fluorescence of tumor was shown 1 hour after injection and became clearest at the 5th hour,then showing a decrescendo trend. Density of QDs surrounding tumor was significantly less than that of QDs-RGD and faded away at the 10th hour. Tumor weight and volume in PDT group,gemcitabine group and combination group were all significantly lower than those in control group and simple illumination group（P〈0. 01）,and those in combination group were significantly lower than those in PDT group and gemcitabine group（P 〈0. 05）. No significant differences in tumor weight and volume were found between control group and simple illumination group（P 〉0. 05）,as well as between PDT group and gemcitabine group（P 〉0. 05）.Tumor inhibition rate in combination group,gemcitabine group and PDT group was 70. 5%,43. 5% and 37. 1%, respectively. Conclusions：QDs-RGD based PDT