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以石墨烯氧化物-明胶载药的伊立替康/叶酸和美洛西林可作为抗癌和抗菌药物开发的新候选

Epirubicin/folic acid and meropenem loaded on graphene oxide-gelatin can be used as a novel candidate for anti-cancer and antibacterial drug development

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发表日期:2024 Dec 05
作者: Mojtaba Ranjbar, Parisa Hashemi Rad, Hajar Rajaei Litkohi, Maryam Solaimani
DOI: 10.1016/j.ijpharm.2024.124846

摘要

美洛西林和伊立替康的耐药性构成了全球性威胁,特别是在医疗资源有限的发展中国家。为克服这一问题,纳米技术提供了多种有前景的解决方案,包括能够提高药物效果的药物递送系统。本研究的目标是首次在SK-OV3癌细胞系中表征包覆明胶(Gel)的石墨烯氧化物(GO)与抗癌药伊立替康(EPi)结合的抗癌机制,并进行叶酸的功能化。此外,将美洛西林加载到石墨烯氧化物-明胶(GO-Gel)中,以提高其疗效。通过FT-IR、XRD、FESEM和EDX等技术对纳米复合材料进行表征。采用MTT法研究GO-Gel、石墨烯氧化物-明胶-叶酸(GO-Gel-FA)、游离Epi和GO-明胶-叶酸/伊立替康(GO-Gel-FA/Epi)纳米复合物对卵巢癌细胞系(SKOV3)与正常卵巢细胞系(HUVEC)细胞的存活率影响。利用qRT-PCR检测GO-Gel-FA/Epi纳米复合物处理细胞中TNFα、Bax、Bcl-2和NF-κB的表达。采用盘扩散法评估游离美洛西林与GO-Gel-美洛西林(GO-Gel-Mer)纳米复合物对两种革兰氏阳性菌和两种革兰氏阴性菌的抗菌活性。结果显示,GO-Gel-FA/Epi纳米复合物对SKOV3细胞表现出比正常HUVEC细胞更强的细胞毒性。Bax的表达上调,而Bcl-2、TNFα和NF-κB在GO-Gel-FA/Epi处理的细胞中表达降低。GO-Gel-Mer纳米复合物在45小时内实现缓释。与游离美洛西林相比,GO-Gel-Mer显示出更强的抗菌活性。GO-Gel-FA/Epi具有强大的抗增殖作用,表现出作为抗癌治疗候选的潜力。新合成的GO-Gel-Mer纳米复合物可作为有效的抗微生物纳米材料,针对多种微生物病原体,包括革兰阴性和革兰阳性菌。

Abstract

Resistance to meropenem and epirubicin poses a significant global threat, particularly in developing nations with constrained health resources. To overcome this problem, nanotechnology provides several promising solutions, including drug delivery systems that can improve the effectiveness of drugs. The objectives of this work is to characterize the anticancer mechanism of Graphene Oxide (GO) coated with Gelatin (Gel) and conjugated with the anticancer drug Epirubicin (EPi), along with functionalization with Folic Acid in SK-OV3 cancer cell lines for the first time. Furthermore, meropenem was loaded onto Graphene Oxide-Gelatin (GO-Gel) to improve its efficacy. The nanocomposites were characterized using FT-IR, XRD, FESEM and EDX. The viability of the ovarian cancer cell lines (SKOV3) and normal ovarian cell lines (HUVEC) after treatment with GO-Gel, Graphene Oxide-Gelatin-Folic acid (GO-Gel-FA), free Epi and Graphene Oxide-Gelatin-Folic acid/ Epirubicin (GO-Gel-FA/Epi) nanocomposite, was studied by the MTT assay. Expression of the TNFα, Bax, Bcl-2, and NF-κB in the GO-Gel-FA/Epi nanocomposite treated cells, were investigated by qRT-PCR. Disc diffusion assay was utilized to assess the antimicrobial activity of free mer and GO-Gel-Mer nanocomposite against two gram-positive bacteria and two gram-negative bacteria. Results demonstrated that The GO-Gel-FA/Epi nanocomposite showed greater cytotoxic effects on SKOV3cells than normal HUVEC cells. The expression of the Bax was upregulated, while the expression of the Bcl-2, TNFα and NF-κB was reduced in GO-Gel-FA/Epi nanocomposite-treated cells. The Graphene Oxide-Gelatin-Meropenem (GO-Gel-Mer) nanocomposite showed a controlled release within 45 h. GO-Gel-Mer nanocomposite showed much more activity against bacteria in comparison to free Mer. GO-Gel-FA/Epi nanocomposite possesses strong anti-proliferative properties against SK-OV3 cancer cells and indicated promising inhibitory candidate for anticancer therapy. The novel synthesized GO-Gel-Mer nanocomposite can be used as an effective antimicrobial nanomaterial against a range of microbial pathogens, including gram-negative and gram-positive bacteria.