壳聚糖温敏凝胶作为卡介苗载体在膀胱肿瘤治疗中的应用研究

Application of Chitosan Hydrogel as a Carrier of Bacillus Calmette-Guérin in the Treatment of Bladder Cancer

目的研究卡介苗的磁性凝胶载体,用以进行膀胱灌注,延长卡介苗在膀胱内的滞留时间,并验证其在膀胱内的抗膀胱肿瘤作用。方法利用大鼠膀胱原位肿瘤动物模型,通过检测相关免疫学及肿瘤学指标评估其抗肿瘤效应。结果与普通卡介苗相比,同等剂量条件下使用卡介苗的磁性凝胶载体可较普通卡介苗在膀胱内产生更多的免疫细胞因子,在膀胱黏膜局部募集淋巴细胞浸润,诱导更强的免疫反应。经验证其抗膀胱肿瘤诱导效果优于普通卡介苗。结论壳聚糖温敏凝胶作为卡介苗载体,在磁场作用下增强了卡介苗的免疫活性及抗肿瘤效应,为卡介苗的应用提供了新的思路,有望成为用于膀胱癌术后灌注预防膀胱癌复发的更好的免疫制剂。

Objective In the former study,we developed a magnetic thermosensitive hydrogel as intravesical BCG delivery system,which was formulated with chitosan (CS),β-glycerophosphate (GP)and Fe3 O4 mag-netic nanoparticle (Fe3 O4 -MNP). The characteristics of the delivery system were determined and it could pro-long intravesical BCG residence time under an applied magnetic field. In this study,the antitumor effect and lo-cal immune activity of BCG loaded magnetic gel was evaluated. Methods The number and volume of tumors was recorded to identify the antitumor activity. Urinary cytokines analysis and immunohistochemistry study were ap-plied to determine the local immunity in bladder. Results In comparison to traditional BCG therapy for superfi-cial bladder tumor,BCG delivered by the gel system markedly increased the antitumor efficacy and induced a high local immunity in bladder. Conclusions The magnetic chitosan hydrogel developed in this work can increase the immunogenic potency of BCG and has great potential for use as a promising intravesical BCG delivery system for superficial bladder cancer.