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基于淀粉样β肽/钌(III)的复合药物的合成与评价及其作为药物递送和抗癌活性的研究

Synthesis and evaluation of amyloid beta peptide/Ruthenium III-based complex drugs as drug delivery and anticancer activity.

作者信息

Senthil Rethinam

机构信息

Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, Tamilnadu 600077, India.

出版信息

Toxicol Rep. 2024 Oct 18;13:101778. doi: 10.1016/j.toxrep.2024.101778. eCollection 2024 Dec.

Abstract

The development and characterization of anticancer complex drugs (ACD), specifically Amyloid Beta Peptide (ABP) - Ruthenium III (Ru III) - nivolumab (NB), were explored through analytical techniques. Fourier-transform infrared (FTIR) spectroscopy demonstrated the structural transformation of peptides from α-helical to β-sheet formations, aligning with amyloid fibril aggregation. Ruthenium (III) complex synthesis was confirmed through distinct absorption peaks in FTIR analysis. High-resolution scanning electron microscopy (HRSEM) revealed the fibrous and smooth morphology of ACD, while thermogravimetric analysis (TGA) confirmed the decomposition stages and stability of the ruthenium complexes. The encapsulation efficiency and in vitro release profile of nivolumab (NB) within ABP-RuIII-NB were investigated, showing a two-phase release over 40 h. Cytotoxicity studies using acridine orange and ethidium bromide staining techniques indicated significant apoptosis in human oral squamous cell carcinoma (OSCC) -treated cells. These findings highlight the potential of ABP-RuIII-NB as an effective cancer treatment with controlled drug release and high cytotoxicity against cancer cells.

摘要

通过分析技术探索了抗癌复合药物(ACD),特别是淀粉样β肽(ABP)-钌(III)(Ru III)-纳武单抗(NB)的研发和特性。傅里叶变换红外(FTIR)光谱表明肽从α-螺旋结构转变为β-折叠结构,这与淀粉样纤维聚集一致。通过FTIR分析中不同的吸收峰证实了钌(III)配合物的合成。高分辨率扫描电子显微镜(HRSEM)揭示了ACD的纤维状和平滑形态,而热重分析(TGA)证实了钌配合物的分解阶段和稳定性。研究了纳武单抗(NB)在ABP-RuIII-NB中的包封效率和体外释放曲线,显示在40小时内呈两相释放。使用吖啶橙和溴化乙锭染色技术进行的细胞毒性研究表明,经治疗的人口腔鳞状细胞癌(OSCC)细胞出现明显凋亡。这些发现突出了ABP-RuIII-NB作为一种有效的癌症治疗方法的潜力,它具有可控的药物释放和对癌细胞的高细胞毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16d1/11532921/e33af6ce2308/gr1.jpg

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