氧化石墨烯-明胶负载的表柔比星/叶酸和美罗培南可作为抗癌和抗菌药物开发的新型候选药物。
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 Oct 16
作者:
Mojtaba Ranjbar, Parisa Hashemi Rad, Hajar Rajaei Litkohi, Maryam Solaimani
来源:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
摘要:
对美罗培南和表柔比星的耐药性构成了重大的全球威胁,特别是在卫生资源有限的发展中国家。为了克服这个问题,纳米技术提供了几种有前景的解决方案,包括可以提高药物有效性的药物输送系统。这项工作的目的是首次表征明胶 (Gel) 包被的氧化石墨烯 (GO) 与抗癌药物表阿霉素 (EPi) 结合的抗癌机制,以及叶酸在 SK-OV3 癌细胞系中的功能化作用。时间。此外,将美罗培南负载到氧化石墨烯明胶(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了表征。使用 GO-Gel、氧化石墨烯-明胶-叶酸 (GO-Gel-FA)、游离 Epi 和氧化石墨烯-明胶-叶酸处理后卵巢癌细胞系 (SKOV3) 和正常卵巢细胞系 (HUVEC) 的活力酸/表柔比星 (GO-Gel-FA/Epi) 纳米复合材料,通过 MTT 测定进行研究。通过 qRT-PCR 研究 GO-Gel-FA/Epi 纳米复合材料处理的细胞中 TNFα、Bax、Bcl-2 和 NF-κB 的表达。采用圆盘扩散测定法评估游离 mer 和 GO-Gel-Mer 纳米复合材料对两种革兰氏阳性菌和两种革兰氏阴性菌的抗菌活性。结果表明,GO-Gel-FA/Epi 纳米复合材料对 SKOV3 细胞表现出比正常 HUVEC 细胞更大的细胞毒作用。在GO-Gel-FA/Epi纳米复合物处理的细胞中,Bax的表达上调,而Bcl-2、TNFα和NF-κB的表达降低。氧化石墨烯-明胶-美罗培南 (GO-Gel-Mer) 纳米复合材料在 45 小时内表现出受控释放。与游离 Mer 相比,GO-Gel-Mer 纳米复合材料表现出更强的抗菌活性。 GO-Gel-FA/Epi 纳米复合材料对 SK-OV3 癌细胞具有很强的抗增殖特性,是有前途的抗癌治疗候选物。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,对抗一系列微生物病原体,包括革兰氏阴性菌和革兰氏阳性菌。版权所有 © 2024。由 Elsevier B.V. 出版。
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.Copyright © 2024. Published by Elsevier B.V.