Kundrapu Durga Bhavani, Rao Podilapu Atchutha, Malla Rama Rao
Cancer Biology Laboratory, Dept of Life Sciences, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India.
Dept of Chemistry, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, Andhra Pradesh, India.
Int J Biol Macromol. 2025 Jan;287:138477. doi: 10.1016/j.ijbiomac.2024.138477. Epub 2024 Dec 10.
Quercetin (QUE) and Taxifolin (TAX) are natural flavonoids with diverse biological activities, holding promise for cancer treatment. However, their clinical application is limited by their poor solubility and bioavailability. Self-assembled bovine serum albumin (BSA) hydrogels have demonstrated biocompatibility and proteolytic stability, making them suitable platforms for drug delivery. The present study validated the anticancer efficacy of QUE, TAX, and DOX encapsulated in BSA hydrogel (QUE@ BSA hydrogel, TAX@ BSA hydrogel, and DOX@ BSA hydrogel), which exhibited 93.5, 90 and 91.2 %% entrapment efficiency, respectively, and controlled release profiles with 90.8,95.8 and 90.8 % drug release, respectively, at lower pH using MDA-MB 231 and MDA-MB 468 TNBC cell lines. Characterization by SEM, XRD, FT-IR and DLS revealed distinctive features of QUE@ BSA hydrogel, TAX@ BSA hydrogel, and DOX@BSA hydrogels, suggesting potential for targeted drug delivery. Further, investigations showed that separate treatment with QUE@BSA hydrogel, TAX@BSA hydrogel, and DOX@BSA hydrogel disrupted cell membrane integrity, akin to inducing cytotoxicity with IC of 12.90, 15.52 and 6.9 μM, respectively, in MDA-MB 231 cells and 16.67, 19.16 and 5.2 μM, respectively, in MDA-MB 468 cells. Moreover, they reduced mammosphere formation and cell migration. Additionally, they induced cell cycle arrest, reduced cell proliferation, and induced apoptosis in TNBC cells. They also induced ROS generation and ER stress, highlighting their potential to suppress TNBC progression. Overall, this study underscores the promise of QUE@ BSA hydrogel and TAX@BSA hydrogel as effective anticancer agents against TNBC cell lines in line with DOX@BSA hydrogel, offering controlled drug release and enhanced therapeutic outcomes.
槲皮素（QUE）和紫杉叶素（TAX）是具有多种生物活性的天然黄酮类化合物，在癌症治疗方面具有前景。然而，它们的临床应用受到其低溶解度和生物利用度的限制。自组装牛血清白蛋白（BSA）水凝胶已证明具有生物相容性和蛋白水解稳定性，使其成为适合药物递送的平台。本研究验证了包裹在BSA水凝胶中的QUE、TAX和DOX（QUE@BSA水凝胶、TAX@BSA水凝胶和DOX@BSA水凝胶）的抗癌功效，其包封率分别为93.5%、90%和91.2%，在较低pH值下使用MDA-MB 231和MDA-MB 468三阴性乳腺癌细胞系时，药物释放率分别为90.8%、95.8%和90.8%，呈现出控释特性。通过扫描电子显微镜（SEM）、X射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）和动态光散射（DLS）进行的表征揭示了QUE@BSA水凝胶、TAX@BSA水凝胶和DOX@BSA水凝胶的独特特征，表明其具有靶向药物递送的潜力。此外，研究表明，分别用QUE@BSA水凝胶、TAX@BSA水凝胶和DOX@BSA水凝胶处理会破坏细胞膜完整性，类似于在MDA-MB 231细胞中分别以12.90、15.52和6.9 μM的半数抑制浓度（IC）诱导细胞毒性，在MDA-MB 468细胞中分别为16.67、19.16和5.2 μM。此外，它们减少了乳腺球形成和细胞迁移。此外，它们诱导细胞周期停滞，降低细胞增殖，并诱导三阴性乳腺癌细胞凋亡。它们还诱导活性氧（ROS）生成和内质网应激，突出了它们抑制三阴性乳腺癌进展的潜力。总体而言，本研究强调了QUE@BSA水凝胶和TAX@BSA水凝胶作为与DOX@BSA水凝胶一致的针对三阴性乳腺癌细胞系的有效抗癌剂的前景，具有控释药物和增强治疗效果的作用。
