Enhanced efficacy of quercetin and taxifolin encapsulated with pH-responsive injectable BSA hydrogel for targeting triple-negative breast cancer cells.

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.