Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery
Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery
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半乳糖基化壳聚糖功能化介孔二氧化硅纳米粒子负载亚叶酸钙用于结肠癌细胞靶向药物输送
DOI：
10.3390/molecules23123082
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发表时间：
2018-12-01
期刊：
影响因子：
4.6
通讯作者：
Pan, Weisan
中科院分区：
文献类型：
--
作者：
Liu, Wei;Wang, Fan;Pan, Weisan
靶向给药结肠癌细胞可显著提高治疗效率。首先通过两步合成法合成了羧基修饰的介孔二氧化硅纳米颗粒（MSN-COOH），然后基于半乳糖化壳聚糖（GC）制备了负载亚叶酸钙（LV）的羧基修饰的介孔二氧化硅纳米颗粒，作为集泌素受体介导的结肠特异性药物递送系统的材料。采用扫描电镜（SEM）、透射电镜（TEM）、x射线衍射（XRD）、傅里叶变换红外（FT-IR）、氮吸附和动态光散射（DLS）对未修饰和功能化的纳米颗粒进行了表征。用紫外分光光度法测定药物的释放特性和载药量。LV@MSN-COOH/GC具有较高的LV载药量，载药量为18.07%。体外以扩散释放为主，为缓释。细胞实验表明，在含有凝集素受体的SW620细胞中，LV@MSN-COOH/GC在体内代谢为甲基四氢叶酸（MTHF）， 5-氟尿嘧啶（5-FU）@MSN-NH2/GC代谢为FdUMP。MTHF和5-氟-2-脱氧尿苷5-单磷酸（FdUMP）联合抑制并显著下调胸苷酸合成酶（TS）的表达。荧光显微镜和流式细胞术实验表明，MSN-COOH/GC具有肿瘤细胞靶向性，能够特异性识别并结合肿瘤细胞中的凝集素受体。结果表明，基于GC的纳米给药系统可以提高LV和5-FU肿瘤细胞的浓度，增强它们对结肠癌的联合作用。
Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN-COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). LV@MSN-COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the LV@MSN-COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN-NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2-deoxyuridine 5-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN-COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.