Dandagi Parineeta, K Yuvaraj Babu, Mary Martin Taniya, K Meenakshi Sundaram
Department of Anatomy, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND.
Cureus. 2024 Sep 13;16(9):e69319. doi: 10.7759/cureus.69319. eCollection 2024 Sep.
This study explores the anticancer potential of Thioflavin-derived zinc nanoparticles (Th-ZnNPs) using both in vitro and in silico methods. Thioflavin, known for its specific binding properties, faces challenges such as bioavailability, rapid metabolism, and solubility. To overcome these limitations and enhance therapeutic efficacy, nanotechnology was utilized to synthesize Th-ZnNPs. These nanoparticles (NPs) are designed to improve drug delivery and effectiveness. The Beclin protein, which plays a critical role in regulating autophagy in cancer cells, was identified as a potential target for these NPs. The study aims to evaluate the interaction between Th-ZnNPs and Beclin protein in glioblastoma cell lines and assess the potential of these NPs as novel anticancer agents.
Th-ZnNPs were synthesized using advanced nanotechnology techniques to improve the bioavailability and solubility of Thioflavin. To explore their anticancer potential, in silico analyses were performed, including molecular docking studies to evaluate the binding affinity between the ZnNPs and Beclin protein, which is integral to autophagy regulation. This computational approach identified the Beclin protein as a promising target for the ZnNPs. Complementary in vitro assays were then conducted, where glioblastoma cell lines (procured from the National Centre for Cell Science, Pune, India) were treated with ZnNPs to assess their cytotoxic effects. The assays also included mechanistic studies to validate the interaction between ZnNPs and Beclin protein and to understand their influence on autophagy pathways.
The synthesis of Th-ZnNPs successfully enhanced their solubility and bioavailability compared to Thioflavin alone. In silico findings showed a strong binding affinity between the Th-ZnNPs and the Beclin protein, suggesting that these NPs may effectively target cancer cells through this interaction. Beclin protein was validated as a relevant target due to its critical role in autophagy regulation. In vitro assays further confirmed the anticancer potential of the Th-ZnNPs, as they exhibited significant cytotoxic effects on glioblastoma cells. Additionally, mechanistic studies revealed that Th-ZnNPs impact Beclin protein and modulate autophagy pathways, supporting their proposed role as effective anticancer agents.
The study highlights the promising anticancer potential of Th-ZnNPs. By overcoming the limitations of Thioflavin through nanotechnology, these NPs show significant therapeutic promise in targeting glioblastoma cells. The strong binding affinity between Th-ZnNPs and the Beclin protein, coupled with confirmed cytotoxic effects, underscores their potential as novel anticancer agents. This integrated approach not only enhances the delivery and efficacy of Thioflavin but also opens new avenues for targeted therapy in glioblastoma treatment.
本研究采用体外和计算机模拟方法探索硫黄素衍生的锌纳米颗粒（Th-ZnNPs）的抗癌潜力。硫黄素以其特定的结合特性而闻名，但面临生物利用度、快速代谢和溶解性等挑战。为克服这些限制并提高治疗效果，利用纳米技术合成了Th-ZnNPs。这些纳米颗粒旨在改善药物递送和有效性。在癌细胞自噬调节中起关键作用的Beclin蛋白被确定为这些纳米颗粒的潜在靶点。本研究旨在评估Th-ZnNPs与胶质母细胞瘤细胞系中Beclin蛋白之间的相互作用，并评估这些纳米颗粒作为新型抗癌药物的潜力。
采用先进的纳米技术合成Th-ZnNPs，以提高硫黄素的生物利用度和溶解性。为探索其抗癌潜力，进行了计算机模拟分析，包括分子对接研究，以评估ZnNPs与Beclin蛋白之间的结合亲和力，Beclin蛋白是自噬调节所必需的。这种计算方法确定Beclin蛋白是ZnNPs的一个有前景的靶点。随后进行了补充性的体外试验，用ZnNPs处理胶质母细胞瘤细胞系（从印度浦那国家细胞科学中心获得），以评估其细胞毒性作用。试验还包括机制研究，以验证ZnNPs与Beclin蛋白之间的相互作用，并了解它们对自噬途径的影响。
与单独的硫黄素相比，Th-ZnNPs的合成成功提高了其溶解性和生物利用度。计算机模拟结果显示Th-ZnNPs与Beclin蛋白之间有很强的结合亲和力，表明这些纳米颗粒可能通过这种相互作用有效地靶向癌细胞。由于Beclin蛋白在自噬调节中的关键作用，它被确认为一个相关靶点。体外试验进一步证实了Th-ZnNPs的抗癌潜力，因为它们对胶质母细胞瘤细胞表现出显著的细胞毒性作用。此外，机制研究表明Th-ZnNPs影响Beclin蛋白并调节自噬途径，支持了它们作为有效抗癌药物的作用。
本研究突出了Th-ZnNPs有前景的抗癌潜力。通过纳米技术克服硫黄素的局限性，这些纳米颗粒在靶向胶质母细胞瘤细胞方面显示出显著的治疗前景。Th-ZnNPs与Beclin蛋白之间的强结合亲和力，加上已证实的细胞毒性作用，强调了它们作为新型抗癌药物的潜力。这种综合方法不仅提高了硫黄素的递送和疗效，也为胶质母细胞瘤治疗中的靶向治疗开辟了新途径。
