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在石墨烯氧化石墨蛋白上加载的表蛋白蛋白/叶酸和叶酸酸酯可以用作抗癌和抗菌药物发育的新型候选者

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

发表日期:2024 Dec 05
作者: Mojtaba Ranjbar, Parisa Hashemi Rad, Hajar Rajaei Litkohi, Maryam Solaimani

摘要

对MeropeNem和半纤维素的抵抗会构成重大的全球威胁,尤其是在发展有限的卫生资源的发展中国家。为了克服这个问题,纳米技术提供了几种有希望的解决方案,包括可以提高药物有效性的药物输送系统。这项工作的目的是表征与明胶(凝胶)涂有氧化石墨烯(GO)的抗癌机制,并与抗癌药物头皮纤维蛋白(EPI)共轭,并首次在SK-OV3癌细胞中与叶酸的功能化。此外,将Meropenem加载到石墨烯氧化石墨蛋白(GO-GEL)上,以提高其功效。使用FT-IR,XRD,FESEM和EDX对纳米复合材料进行表征。卵巢癌细胞系(SKOV3)和正常卵巢细胞系(HUVEC)的生存能力在用GO-GEL,氧化石墨烯氧化物 - 氧化素 - 含量酸(GO-GEL-FA),FREE EPI和氧化石墨烯 - 氧化物 - 氧化物 - 氧化物 - 羟基 - 含氧蛋白 - 纤维酸/ co-gel-fa/ epi-epi/ Epi)NANANOMOMPOSITES进行了研究。 QRT-PCR研究了TNFα,BAX,BCL-2和NF-κB在GO-GEL-FA/EPI纳米复合材料处理的细胞中的表达。椎间盘扩散测定法用于评估游离MER和GO-GEL-MER纳米复合材料对两种革兰氏阳性细菌和两个革兰氏阴性细菌的抗菌活性。结果表明,与正常的HUVEC细胞相比,Go-Gel-FA/Epi纳米复合材料对SKOV3细胞的细胞毒性作用更大。 BAX的表达上调,而在GO-GEL-FA/EPI纳米复合材料处理的细胞中,Bcl-2,TNFα和NF-κB的表达降低。石墨烯氧化物明智的 - 梅焦(GO-GEL-MER)纳米复合材料在45小时内显示出受控释放。与Free MER相比,Go-Gel-Mer纳米复合材料对细菌的活性更多。 Go-Gel-Fa/Epi纳米复合材料具有针对SK-ov3癌细胞的强抗增殖特性,并表明有前途的抗癌抑制作用。新型合成的Go-Gel-Mer纳米复合材料可用作有效的抗菌纳米材料,以针对一系列微生物病原体,包括革兰氏阴性菌和革兰氏阳性细菌。

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.