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Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics
Biomedical Materials ( IF 4 ) Pub Date : 2024-02-15 , DOI: 10.1088/1748-605x/ad2407
Dwaipayan Bhattacharya , Madhu Rani Bharati , Kalyani Sakhare , Piyush Khandelia , Rajkumar Banerjee , Kumar Pranav Narayan

Glucocorticoid and Mineralocorticoid receptors are principally ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. Our study investigates the potential of these receptors to act as a target for oral cancer treatment since findings in this regard are sparse till date. Leveraging the aberrant behavior of steroid hormone receptors (SHRs) in cancer, we have targeted oral cancer cells in 2D-culture using liposomes containing both synthetic as well as crude, natural SHR ligands isolated from an aqueous Indian medicinal plant. Lipoplexes thus formulated demonstrated targeted transfectability as indicated by expression of green fluorescent protein. Transfection of oral squamous cell carcinoma cells with exogenous, anticancer gene p53 lipoplexed with crude saponin-based liposome induced apoptosis of cancer cells via regulation of BAX and B-cell leukemia/lymphoma-2 (BCL2) protein levels at levels comparable with pre-established delivery systems based on synthetic SHR ligands. Our findings strongly indicate a possibility of developing plant saponin-based inexpensive delivery systems which would target cancer cells selectively with reduced risks of off target delivery and its side effects.

中文翻译:

基于类固醇激素受体的基因传递系统作为潜在的口腔癌治疗方法

糖皮质激素和盐皮质激素受体主要是配体依赖性细胞内转录因子,已知它们会影响许多人类癌症的发生和生长。我们的研究调查了这些受体作为口腔癌治疗靶点的潜力,因为迄今为止这方面的研究结果很少。利用类固醇激素受体 (SHR) 在癌症中的异常行为,我们使用脂质体在 2D 培养中靶向口腔癌细胞,该脂质体含有从印度水性药用植物中分离出的合成和粗天然 SHR 配体。由此配制的脂质复合物表现出靶向转染性,如绿色荧光蛋白的表达所示。用基于粗皂苷的脂质体脂质体复合的外源抗癌基因 p53 转染口腔鳞状细胞癌细胞,通过调节 BAX 和 B 细胞白血病/淋巴瘤 2 (BCL2) 蛋白水平至与预先确定的水平相当,诱导癌细胞凋亡基于合成 SHR 配体的递送系统。我们的研究结果强烈表明开发基于植物皂苷的廉价递送系统的可能性,该系统可以选择性地靶向癌细胞,并降低脱靶递送及其副作用的风险。
更新日期:2024-02-15
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