7-Amino-6H-anthra[9,1-cd] Isothiazol-6-one-Casein Nanosystem for Live Cell Staining and Augmenting Therapeutic Effectiveness in Triple Negative Breast Cancer,ACS Applied Nano Materials

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7-Amino-6H-anthra[9,1-cd] Isothiazol-6-one-Casein Nanosystem for Live Cell Staining and Augmenting Therapeutic Effectiveness in Triple Negative Breast Cancer
ACS Applied Nano Materials ( IF 5.3 ) Pub Date : 2024-02-14 , DOI: 10.1021/acsanm.4c00594
Sajmina Khatun ₁ , Vivekshinh Kshtriya ₂ , Nidhi Gour ₂ , Kavipriya Murugaiyan ₁ , Aravind Kumar Rengan ₁

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Triple negative breast cancer (TNBC) causes a significant challenge in oncology due to its aggressive nature and limited treatment options. This study introduces a promising strategy to enhance therapeutic effectiveness against TNBC by developing a dual-functioning 7-amino-6H-anthra[9,1-cd] isothiazol-6-one (AAT) encapsulated Casein nanosystem (CAAT NPs). This innovative approach serves both as a live cell staining technique and as a means to augment therapeutic outcomes in highly metastatic TNBC. AAT, chosen for its dual role as a fluorescence marker for live cells and its inherent anticancer properties, undergoes fluorescence quenching upon inducing cancer cell death. The Casein nanosystem ensures efficient dye encapsulation, providing stability and controlled release. Physicochemical analysis validates successful encapsulation, yielding a desirable size distribution of CAAT NPs. Cellular uptake studies demonstrate effective internalization in 4T1 cells with minimal cytotoxicity in healthy cell lines and organisms. Subsequent investigations revealed subcellular localization, altered mitochondrial membrane potential, nucleus breakage, antimigration activity, and growth suppression in 4T1 cells. Increased expression of γH2AX, indicating DNA damage, further underscores the therapeutic potential. In a 3-D model of 4T1 cells, CAAT NPs exhibit significant therapeutic efficacy, suggesting a promising option for safe and efficient TNBC treatment.

中文翻译：

7-氨基-6H-anthra[9,1-cd]异噻唑-6-一酪蛋白纳米系统用于活细胞染色和增强三阴性乳腺癌的治疗效果

三阴性乳腺癌（TNBC）因其侵袭性和有限的治疗选择而给肿瘤学带来了重大挑战。这项研究引入了一种有前途的策略，通过开发双功能的 7-氨基-6H-蒽[9,1-cd]异噻唑-6-酮 (AAT) 封装酪蛋白纳米系统 (CAAT NPs) 来增强 TNBC 的治疗效果。这种创新方法既可作为活细胞染色技术，又可作为增强高度转移性 TNBC 治疗效果的手段。 AAT 因其作为活细胞荧光标记物的双重作用及其固有的抗癌特性而被选中，在诱导癌细胞死亡时会经历荧光猝灭。酪蛋白纳米系统确保有效的染料封装，提供稳定性和受控释放。物理化学分析验证了成功的封装，产生了理想的 CAAT 纳米颗粒尺寸分布。细胞摄取研究表明，4T1 细胞可有效内化，而对健康细胞系和生物体的细胞毒性极小。随后的研究揭示了 4T1 细胞中的亚细胞定位、线粒体膜电位改变、细胞核断裂、抗迁移活性和生长抑制。 γH2AX 表达增加表明 DNA 损伤，进一步强调了治疗潜力。在 4T1 细胞的 3D 模型中，CAAT NP 表现出显着的治疗功效，这表明它是安全有效的 TNBC 治疗的有希望的选择。

更新日期：2024-02-14

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