MB-SF/cRGD的合成及其化学动力学抗肿瘤研究  

Synthesis of MB-SF/cRGD for Antitumor Chemodynamic Therapy

作　　者：张兴莉 焦晓丹 于云龙 钟莉[3] 康跃军[1] 薛鹏[1] ZHANG Xingli;JIAO Xiaodan;YU Yunlong;ZHONG Li;KANG Yuejun;XUE Peng(School of Materials and Energy,Southwest University,Chongqing 400715,China;Burns Research Institute,The First Affiliated Hospital of the Army Medical University,Chongqing 400038,China;School of Bioengineering,Chongqing University,Chongqing 400044,China)

机构地区：[1]西南大学材料与能源学院,重庆400715 [2]陆军军医大学第一附属医院烧伤研究所,重庆400038 [3]重庆大学生物工程学院,重庆400044

出　　处：《西南大学学报（自然科学版）》2024年第6期51-62,共12页Journal of Southwest University(Natural Science Edition)

基　　金：重庆市鲁渝科技协作项目(CSTB2023TIAD-LDX0015);国家自然科学基金项目(32071375);重庆市高等教育教学改革研究项目(223079);国家重点研发计划项目(2023YFF0713900);宜宾市双城协议保障科研经费科技项目(XNDX2022020013).

摘　　要：化学动力学治疗(CDT)具有一定的抗肿瘤效果,但由于肿瘤微环境(TME)的复杂性,导致药物无法高效积聚到肿瘤部位,从而无法达到满意的治疗效果.先通过水解与提纯得到丝素蛋白,再通过酰胺化反应在丝素蛋白表面连接cRGD,最后加入Bi(NO_(3))·5H_(2)O和MnCl_(2)·4H_(2)O,搅拌过夜获得MB-SF/cRGD.设计了一种具有主动靶向能力的CDT治疗体系,旨在通过提高癌症细胞药物摄取率,加强化学动力学治疗效果.丝素蛋白作为一种具有良好生物相容性和降解性的药物载体,可以有效改善药物递送系统引起的生物相容性差等问题;MnO_(2)利用内源性H_(2)O_(2)实现化学动力学治疗、消耗GSH以及产生O_(2),发挥抗肿瘤疗效.此外,在药物表面修饰cRGD不但可以减少对正常细胞的毒性,还可以提高化学动力学治疗的价值.实验结果表明:利用MB-SF本身的活性能达到一定的抗肿瘤疗效,在此基础上,修饰有主动靶向癌细胞的cRGD所获得的MB-SF/cRGD能达到更好的肿瘤治疗效果.Chemodynamic therapy(CDT)has shown some therapeutic effects toward tumors,but due to the complexity of the tumor microenvironment(TME),the drugs do not accumulate efficiently at the tumor site,thus failing to achieve a satisfactory therapeutic effect.In this study,silk fibroin was obtained by hydrolysis and purification.Then,cRGD was attached to the surface of the fibroin protein by amidation reaction.Finally,Bi(NO_(3))·5H_(2)O and MnCl_(2)·4H_(2)O were added and stirred overnight to obtain MB-SF/cRGD.A hybrid system with active targeting ability was designed to enhance the therapeutic effect of CDT by increasing the cellular uptake rate of nanodrug.As drug carriers with good biocompatibility and degradability,silk fibroin can effectively improve the biocompatibility and other safety issues caused by drug delivery system.MnO_(2)utilizes endogenous H_(2)O_(2)for triggering CDT,GSH depletion and O_(2)production to promote antitumor efficacy.In addition,the modified cRGD on the drug surface reduces toxicity to normal cells and increases the efficacy of CDT.Experimental results show that MB-SF alone can achieve a certain level of antitumor effect,but an improved tumor treatment effect can be achieved by MB-SF/cRGD,due to the modified cRGD can actively target the cancer cells.

关 键 词：化学动力学治疗 肿瘤微环境 靶向治疗 活性氧 

分 类 号：R737.9[医药卫生—肿瘤]