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通过以下方法合成的生物源氧化锌纳米颗粒:对NG-108胶质母细胞瘤细胞的选择性细胞毒性。

Biogenic ZnO Nanoparticles Synthesized by : A Selective Cytotoxicity Against NG-108 Glioblastoma Cells.

作者信息

Quispe Cohaila Alberto Bacilio, Fora Quispe Gabriela de Lourdes, Cáceda Quiroz César Julio, Mamani Anccasi Roxana, Mejía García Telmo Agustín, Tamayo Calderón Rocío María, Gamarra Gómez Francisco, Sacari Sacari Elisban Juani

机构信息

Grupo de Investigación GIMAECC, Facultad de Ingeniería, Universidad Nacional Jorge Basadre Grohmann, Avenida Miraflores S/N, Ciudad Universitaria, Tacna 23003, Peru.

Escuela de Metalurgia y Materiales, Facultad de Ingeniería, Universidad Nacional Jorge Basadre Grohmann, Avenida Miraflores S/N, Ciudad Universitaria, Tacna 23003, Peru.

出版信息

Nanomaterials (Basel). 2025 Aug 31;15(17):1338. doi: 10.3390/nano15171338.

Abstract

Glioblastoma multiforme (GBM) remains the most aggressive primary brain tumor with median survival of 14.6 months, necessitating novel therapeutic approaches. Here, we report the biogenic synthesis of zinc oxide nanoparticles (ZnO NPs) using strain TT14s isolated from mining environments and demonstrate their selective anti-glioma efficacy. ZnO NPs exhibited hexagonal wurtzite structure (crystallite size: 15.48 nm) with spherical morphology (19.37 ± 5.28 nm diameter) as confirmed by XRD, HRTEM, and comprehensive physicochemical characterization. Colloidal stability analysis revealed an isoelectric point at pH 7.46, ensuring optimal dispersion in biological media. Cytotoxicity evaluation revealed remarkable selectivity: at 100 μg/mL, ZnO NPs reduced NG-108 glioblastoma cell viability to 36.07 ± 1.89% within 1 h while maintaining 78.9 ± 0.94% viability in primary retinal cells. The selective cytotoxicity was attributed to the interplay of convergent mechanisms acting under dark conditions, including defect-mediated ROS generation supported by photoluminescence analysis revealing a characteristic oxygen vacancy emission at 550 nm, pH-dependent dissolution enhanced in the acidic tumor microenvironment, and preferential cellular uptake by rapidly proliferating cancer cells with compromised antioxidant defenses. Time-course analysis demonstrated concentration-dependent effects with therapeutic windows favoring normal cell preservation. The intrinsic cytotoxic activity under dark laboratory conditions eliminates the need for external activation, providing practical advantages for therapeutic applications. These findings establish ZnO NPs as promising candidates for targeted glioblastoma therapy, warranting further in vivo validation and mechanistic elucidation for clinical translation.

摘要

多形性胶质母细胞瘤(GBM)仍然是最具侵袭性的原发性脑肿瘤,中位生存期为14.6个月,因此需要新的治疗方法。在此,我们报告了使用从采矿环境中分离出的TT14s菌株生物合成氧化锌纳米颗粒(ZnO NPs),并证明了它们的选择性抗胶质瘤功效。XRD、HRTEM和全面的物理化学表征证实,ZnO NPs呈现六方纤锌矿结构(微晶尺寸:15.48 nm),形态为球形(直径19.37±5.28 nm)。胶体稳定性分析显示其等电点为pH 7.46,确保在生物介质中最佳分散。细胞毒性评估显示出显著的选择性:在100μg/mL时,ZnO NPs在1小时内将NG-108胶质母细胞瘤细胞活力降低至36.07±1.89%,而原代视网膜细胞的活力保持在78.9±0.94%。这种选择性细胞毒性归因于在黑暗条件下起作用的多种机制的相互作用,包括光致发光分析支持的缺陷介导的活性氧生成,该分析揭示了在550 nm处的特征性氧空位发射、在酸性肿瘤微环境中增强的pH依赖性溶解,以及抗氧化防御受损的快速增殖癌细胞的优先细胞摄取。时间进程分析表明存在浓度依赖性效应,治疗窗口有利于正常细胞的保存。在黑暗实验室条件下的内在细胞毒性活性无需外部激活,为治疗应用提供了实际优势。这些发现确立了ZnO NPs作为靶向胶质母细胞瘤治疗的有前景的候选物,值得进一步进行体内验证和机制阐释以实现临床转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12d0/12430215/7c40b59f1e5c/nanomaterials-15-01338-g001.jpg

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