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生物合成的氧化铜纳米颗粒和负载5-氟尿嘧啶的抗癌凝胶用于HeLa宫颈癌细胞。

Biogenic synthesized CuO nanoparticles and 5-fluorouracil loaded anticancer gel for HeLa cervical cancer cells.

作者信息

Dutta Gouranga, Chinnaiyan Santhosh Kumar, Palaniyandi Thirunavukkarasu, Sugumaran Abimanyu, Narayanasamy Damodharan

机构信息

Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India.

Department of Pharmaceutics, Rajiv Gandhi Institute of Pharmaceutical Sciences and Research (RPISAR), Trikaripur, Kasargod, Kerala, 671310, India.

出版信息

Discov Nano. 2024 Dec 27;19(1):217. doi: 10.1186/s11671-024-04166-7.

Abstract

Cervical cancer remains a significant health challenge in developing countries are high due to low HPV vaccination rates, delayed diagnosis, and restricted healthcare access. Metal nanomaterials, such as copper oxide (CuO) nanoparticles (NPs), have shown significant promise in cancer therapy due to their ability to induce apoptosis. 5-Fluorouracil (5-Fu) enhances the cytotoxic effect against cervical cancer, working synergistically with CuO NPs to maximize the therapeutic impact while potentially reducing the 5-Fu's systemic side effects. This study explores the synergistic therapeutic potential of green-synthesized CuO NPs combined with 5-Fu in a gel formulation for targeted anticancer activity against HeLa cervical cancer cells. CuO NPs were synthesized using Trichosanthes dioica dried seeds extract and incorporated into a pectin-xanthan gum-based gel. The green-synthesized CuO NPs exhibited a zeta potential of -23.7 mV, a particle size of approximately 26 nm, and spherical morphology. Characterization studies, including FTIR, viscosity, spreadability, pH, and stability assessments, confirmed the gel's suitability for vaginal delivery. In-vitro drug release showed xanthan gum extended the release up to 8 h. The MTT assay revealed PXFCu6 gel's IC at 11.82 ± 0.22 μg/mL, significantly more cytotoxic to HeLa cells, being 3.62 times potent than CuO NPs (IC: 42.8 ± 0.24 μg/mL) and 1.63 times potent than 5-Fu alone (IC: 19.3 ± 0.49 μg/mL). The antibacterial assay showed no inhibition for the plain gel, but T. dioica-mediated CuO NPs exhibited inhibition of 22.35 ± 4.9 mm. PXFCu6 gel had the more potent inhibition at 52.05 ± 1.37 mm against Escherichia coli growth. The PXFCu6 gel showed better stability at 4 °C, maintaining viscosity, pH, and drug release, unlike 25 °C where a mild degradation occurred. This research highlights the potential of the CuO NPs-5-Fu gel as a novel, effective therapeutic strategy for cervical cancer treatment.

摘要

由于人乳头瘤病毒(HPV)疫苗接种率低、诊断延迟以及医疗保健机会有限,宫颈癌在发展中国家仍然是一项重大的健康挑战。金属纳米材料,如氧化铜(CuO)纳米颗粒(NPs),因其诱导细胞凋亡的能力,在癌症治疗中显示出巨大的前景。5-氟尿嘧啶(5-Fu)增强了对宫颈癌的细胞毒性作用,与CuO NPs协同作用,以最大化治疗效果,同时可能降低5-Fu的全身副作用。本研究探讨了绿色合成的CuO NPs与5-Fu在凝胶制剂中的协同治疗潜力,以实现对人乳头瘤病毒(HeLa)宫颈癌细胞的靶向抗癌活性。使用栝楼干燥种子提取物合成CuO NPs,并将其掺入基于果胶-黄原胶的凝胶中。绿色合成的CuO NPs的zeta电位为-23.7 mV,粒径约为26 nm,呈球形形态。包括傅里叶变换红外光谱(FTIR)、粘度、铺展性、pH值和稳定性评估在内的表征研究证实了该凝胶适用于阴道给药。体外药物释放表明,黄原胶将释放时间延长至8小时。MTT法显示PXFCu6凝胶的半数抑制浓度(IC)为11.82±0.22μg/mL,对HeLa细胞的细胞毒性显著更高,效力是CuO NPs(IC:42.8±0.24μg/mL)的3.62倍,是单独使用5-Fu(IC:19.3±0.49μg/mL)的1.63倍。抗菌试验表明,普通凝胶无抑制作用,但栝楼介导的CuO NPs对大肠杆菌的抑菌圈直径为22.35±4.9 mm。PXFCu6凝胶对大肠杆菌生长的抑制作用更强,抑菌圈直径为52.05±1.37 mm。与25℃时发生轻微降解不同,PXFCu6凝胶在4℃时表现出更好的稳定性,能维持粘度、pH值和药物释放。本研究突出了CuO NPs-5-Fu凝胶作为一种新型、有效的宫颈癌治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386c/11680562/52b127144377/11671_2024_4166_Fig1_HTML.jpg

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