Page 84 - 《精细化工》2021年第9期

第 38 卷第 9 期 精 细 化 工 Vol.38, No.9
202 1 年 9 月 FINE CHEMICALS Sept. 2021

功能材料
构建 pH 响应性中空介孔硅纳米复合材料

用于肿瘤联合治疗

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海国冉，程崟家 ，张爱清
（中南民族大学 化学与材料科学学院，湖北 武汉 430074）

摘要：以正硅酸四乙酯为原料，合成直径约为 100 nm 的中空介孔二氧化硅纳米颗粒（HMSN）作为药物载体，
采用物理包埋法和原位还原 KMnO 4 生成二氧化锰的方法实现对化疗药物阿霉素（DOX）和 MnO 2 的有效负载。
此外，利用肿瘤靶向性功能肽（PEG-R 7 -RGDS）末端的氨基与醛基修饰的 HMSN（HMSN-CHO）形成席夫碱，
合成 pH 响应性纳米载药系统（DOX/MnO 2 @HMSN-imide-PEG-R 7 -RGDS）。通过 TEM、激光粒度仪、FTIR 和
XRD 对合成材料形貌、粒径、结构和组成等进行表征。结果表明，合成的 HMSN 呈球形中空结构。
DOX/MnO 2 @HMSN-imide-PEG-R 7 -RGDS 在模拟的肿瘤酸性环境（pH 5.0）中具有明显快于在模拟生理环境
（pH 7.4）下的药物释放行为。此外，体外细胞实验结果表明，DOX/MnO 2 @HMSN-imide-PEG-R 7 -RGDS 可以
靶向进入宫颈癌细胞（HeLa）并快速释放 DOX。与此同时，纳米载药颗粒中的 MnO 2 和肿瘤细胞中高浓度谷胱
2+
2+
甘肽（GSH）反应产生具有类芬顿反应效果的 Mn 。Mn 与肿瘤细胞内过表达的 H 2 O 2 反应生成•OH，发挥增
强的化学动力学治疗。细胞毒性实验证明，化学动力学治疗与化疗相结合能对 HeLa 细胞产生很高的细胞毒性。
关键词：肿瘤靶向；功能性多肽；化疗/化学动力学联合治疗；中空介孔二氧化硅；药物可控释放；功能材料
中图分类号：TB383；Q279 文献标识码：A 文章编号：1003-5214 (2021) 09-1798-10

Construction of pH-responsive HMSN nanocomposites

for combinatory therapy of tumor

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HAI Guoran, CHENG Yinjia , ZHANG Aiqing
（School of Chemistry and Materials Science, South-Centre University for Nationalities, Wuhan 430074, Hubei, China）

Abstract: Hollow mesoporous silica nanoparticles (HMSN) with a diameter of about 100 nm were
fabricated from tetraethyl orthosilicate. HMSN were used as drug nanocarrier to load chemotherapeutic
drug doxorubicin (DOX) and manganese dioxide by physical embedding method and in situ reduction of
KMnO 4 to produce manganese dioxide. Then, a pH-responsive nano-drug delivery system (DOX/MnO 2@
HMSN-imide-PEG-R 7-RGDS) was constructed by forming Schiff base between tamino group at the
terminal of tumor-targeting functional peptide (PEG-R 7-RGDS) and the aldehyde-modified HMSN
(HMSN-CHO). The morphology, particle size, structure and composition of the nanomaterials were
characterized by TEM, laser particle size analyzer, FTIR and XRD. The results showed that the synthesized
spherical HMSN possessed hollow nanostructure. DOX/MnO 2 @HMSN-imide-PEG-R 7 -RGDS nanoparticles
exhibited higher drug release rate under the simulated acidic tumor environment (pH 5.0) than that in the
simulated physiological environment (pH 7.4). In addition, the results of in vitro cell experiments indicated
that DOX/MnO 2@HMSN-imide-PEG-R 7-RGDS could target to cervical cancer cells (HeLa) and release
DOX efficiently. At the same time, MnO 2 in drug loaded nanoparticles reacted with high concentration of
2+
2+
glutathione (GSH) in tumor cells to produce Mn with Fenton-like effect. Subsequently, Mn reacts with
the over-expression H 2O 2 in tumor cells to produce •OH, exerting enhanced chemo dynamic therapy. The

收稿日期：2021-02-18; 定用日期：2021-05-18; DOI: 10.13550/j.jxhg.20210172
基金项目：国家自然科学基金（51703251）
作者简介：海国冉（1996—），男，硕士生，E-mail：1241539045@qq.com。联系人：程崟家（1988—），女，讲师，E-mail：ChengYJ@
mail.scuec.edu.cn；张爱清（1963—），男，教授，E-mail：123269698@qq.com。