摘要
目的探讨携载葡萄糖氧化酶的富含锰介孔硅纳米(MSN@Mn-GOx)的制备、物化表征及其治疗胃肠道恶性肿瘤的效果。方法检测MSN@Mn-GOx的形貌、大小、元素、价态、电位、耗氧能力及类芬顿性能;采用核磁共振成像(MRI)方法分析MSN@Mn-GOx在T1加权下的成像能力,构建荷瘤小鼠肠癌模型(n=3),通过尾静脉注射MSN@Mn-GOx观察注射前后的T1成像能力;体外试验分为Control组(PBS)、含锰介孔硅(MSN@Mn)组(20μg/mL MSN@Mn纳米颗粒)及携载葡萄糖氧化酶的富含锰介孔硅(MSN@Mn-GOx)组(20μg/mL MSN@Mn-GOx纳米颗粒),按上述分组对胃肠癌细胞进行处理。分别采用细胞增殖-毒性实验(CCK-8)、细胞免疫荧光实验检测MSN@Mn-GOx诱导胃肠癌细胞的活性氧(ROS)生成、细胞增殖及细胞杀伤能力的改变。结果MSN@Mn-GOx为带负电荷的100 nm类圆形实心纳米颗粒,可催化葡萄糖产生大量氧气继而增加H2O2浓度。相比于中性H2O2溶液,MSN@Mn-GOx在低酸条件(pH=6.0)下可催化生成更多羟自由基(P<0.05)。MRI成像试验中,MSN@Mn-GOx有浓度依赖性的T1增强成像效果,在荷瘤小鼠体内观察到,相比于注射前,注射MSN@Mn-GOx后的瘤体有T1增强信号(P<0.01)。细胞免疫荧光实验显示:相比于Control组,MSN@Mn及MSN@Mn-GOx均可明显诱导胃肠癌细胞ROS产生(P<0.05)。CCK-8实验显示,相比于Control组,MSN@Mn及MSN@Mn-GOx对胃肠癌细胞浓度依赖性杀伤效果(P<0.05)。Edu实验显示,相比于Control组,MSN@Mn及MSN@Mn-GOx均可抑制胃肠癌细胞的增殖能力(P<0.05)。结论MSN@Mn-GOx具有良好的MRI成像效果、自产H2O2能力及类芬顿性能,可诱导胃肠癌细胞内ROS产生进而产生良好的抗肿瘤效应,是胃肠道恶性肿瘤治疗的一种潜在新方法。
Objective To investigate the physicochemical features of glucose oxidase-loaded and manganese-based mesoporous silica nanoparticles(MSN@Mn-GOx)and its antitumor effect against gastrointestinal cancer.Methods The morphology,particle size and Fenton-like properties of MSN@Mn-GOx nanoparticles were analyzed using transmission electron microscopy(TEM),dynamic light scattering(DLS),Zeta potential analysis,ultraviolet absorption spectroscopy,energy dispersive spectroscopy and X-ray photoelectron spectroscopy.A mouse model bearing human colon cancer HT-29 xenograft was established to examine the antitumor effect of MSN@Mn-GOx using MRI imaging.Reactive oxygen species(ROS)production assay,CCK-8 assay and EdU assay were used to evaluate the in vitro anti-tumor effect of the nanoparticles.Results MSN@Mn-GOx nanoparticles were solid spheres with a diameter of about 100 nm and a Zeta potential of-35 mV.MSN@Mn GOx had a higher H2O2 catalytic efficiency in glucose containing solution than in glucose-free solution,and showed a stronger Fenton-like properties at pH6.0 than at pH7.4(P<0.05).In the tumor-bearing mice,MSN@Mn-GOx treatment dose-dependently enhanced T1 imaging of the tumor(P<0.01).Compared with the control group and MSN@Mn group,MSN@Mn-GOx induced a significantly higher level of ROS production and a stronger inhibitory effect on the proliferation of gastric and colon cancer cells(P<0.05).Conclusion MSN@Mn-GOx nanoparticles have good chemodynamic properties and a strong anti-tumor effect and provide a potential therapeutic option for gastric cancer.
作者
林晓丰
黄马养
陈君千
周逊
钟卓丹
陆文聪
黄显莹
刘添文
LIN Xiaofeng;HUANG Mayang;CHEN Junqian;ZHOU Xun;ZHONG Zhuodan;LU Wencong;HUANG Xianying;LIU Tianwen(Department of Spleen and Stomach Diseases,Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510515,China;Department of Pediatrics,Guangdong Women and Children's Hospital,Guangzhou 510515,China;Department of Vascular Interventional Therapy,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2023年第8期1432-1439,共8页
Journal of Southern Medical University
基金
广东省自然科学基金(2020B1515120045,2020A1515110151)。
关键词
锰基纳米材料
纳米颗粒
胃肠道肿瘤
化学动力治疗
manganese-based nanomaterials
nanoparticles
gastrointestinal cancer
chemodynamic therapy
