利用双敏感智能纳米复合材料增强顺铂向肝癌 HepG2 细胞的递送。

Enhancing cisplatin delivery to hepatocellular carcinoma HepG2 cells using dual sensitive smart nanocomposite.

机构信息

a Department of Chemistry, Faculty of Science , Urmia University , Urmia , Iran.

b Department of Medical Biotechnology, Faculty of Advanced Medical Sciences , Tabriz University of Medical Sciences , Tabriz , Iran.

出版信息

Artif Cells Nanomed Biotechnol. 2018 Aug;46(5):949-958. doi: 10.1080/21691401.2017.1349777. Epub 2017 Jul 7.

Abstract

Targeted entrance and accumulation of higher doses of drugs into malignant cells could help in intensification of tumor specific cytotoxicity. A dual-responsive nanogel, poly(N-isopropylacrylamide)-co-poly(N,N-(dimethylamino)ethyl methacrylate) [P(NIPAM-co-DMA)] containing N-isopropylacrylamide (NIPAM) as thermoresponsive monomer and N,N-(dimethylamino)ethyl methacrylate (DMA) as pH-responsive monomer and methylene-bis-acrylamide (MBA) as cross-linking agent, was synthesized by free radical emulsion polymerization. Cisplatin along with magnetic FeO nanoparticles (MNPs) was loaded into the nanogel by physically embedding the magnetic nanoparticles into hydrogel matrix after gelation to obtain drug-loaded magnetic nanocomposite [P(NIPAM-co-DMA)/FeO]. Drug loading efficiencies and drug release profiles of cisplatin-loaded P(NIPAM-co-DMA) nanogel and P(NIPAM-co-DMA)/FeO nanocomposite were evaluated in vitro for controlled drug delivery in different temperature and pH conditions. Finally, the anticancer activity of P(NIPAM-co-DMA)/FeO nanocomposite on human liver HepG2 cells was evaluated. Nanogel and nanocomposite showed significantly higher (p < .05) cisplatin release at 40 °C compared to 37 °C and at pH 5.7 compared to pH 7.4, demonstrating their temperature and pH sensitivity, respectively. The cytotoxicity assay of drug free nanogel on HepG2 cell line indicated that the nanogel is biocompatible and suitable as drug carrier. Moreover, MTT assay revealed that the cisplatin-loaded nanocomposite represented significant superior cytotoxicity (p < .05) to HepG2 cells as compared with free cisplatin.

摘要

靶向进入和积累更高剂量的药物进入恶性细胞可以帮助增强肿瘤特异性细胞毒性。一种双重响应纳米凝胶,聚(N-异丙基丙烯酰胺)-共-聚(N,N-(二甲氨基)乙基甲基丙烯酸酯)[P(NIPAM-co-DMA)],含有 N-异丙基丙烯酰胺(NIPAM)作为温敏单体和 N,N-(二甲氨基)乙基甲基丙烯酸酯(DMA)作为 pH 响应单体和亚甲基双丙烯酰胺(MBA)作为交联剂,通过自由基乳液聚合合成。顺铂与磁性 FeO 纳米粒子(MNPs)通过在凝胶化后将磁性纳米粒子物理嵌入水凝胶基质中被负载到纳米凝胶中,以获得载药磁性纳米复合材料[P(NIPAM-co-DMA)/FeO]。体外评估载顺铂的 P(NIPAM-co-DMA)纳米凝胶和 P(NIPAM-co-DMA)/FeO 纳米复合材料的载药效率和药物释放曲线,以在不同温度和 pH 条件下进行控制药物释放。最后,评估 P(NIPAM-co-DMA)/FeO 纳米复合材料对人肝癌 HepG2 细胞的抗癌活性。纳米凝胶和纳米复合材料在 40°C 下比在 37°C 下和在 pH 5.7 下比在 pH 7.4 下显示出明显更高(p < .05)的顺铂释放,分别证明了它们的温度和 pH 敏感性。药物无纳米凝胶对 HepG2 细胞系的细胞毒性试验表明,纳米凝胶具有生物相容性,适合作为药物载体。此外,MTT 测定表明,与游离顺铂相比,载顺铂的纳米复合材料对 HepG2 细胞表现出显著更高的细胞毒性(p < .05)。

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