南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (8): 1432-1439.doi: 10.12122/j.issn.1673-4254.2023.08.22

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锰基纳米材料用于胃肠道恶性肿瘤的化学动力治疗

林晓丰，黄马养，陈君千，周 逊，钟卓丹，陆文聪，黄显莹，刘添文   

  1. 广州中医药大学第二附属医院脾胃病科，广东 广州 510515；广东省妇幼保健院儿科，广东 广州 510515；南方医科大学南方医院血管介入科，广东 广州 510515
  • 出版日期:2023-08-20 发布日期:2023-09-13

Manganese-based nanoparticles for chemodynamic therapy of gastrointestinal cancer

LIN Xiaofeng, HUANG Mayang, CHEN Junqian, ZHOU Xun, ZHONG Zhuodan, LU Wencong, HUANG Xianying, LIU Tianwen   

  1. 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
  • Online:2023-08-20 Published:2023-09-13

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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（20 μg/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（20 μg/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。

关键词: 锰基纳米材料；纳米颗粒；胃肠道肿瘤；化学动力治疗

Abstract: 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.

Key words: manganese-based nanomaterials; nanoparticles; gastrointestinal cancer; chemodynamic therapy