Jujube Peel Pigment-Loaded Thermosensitive Hydrogel with In Vitro Pro-Apoptotic and Antibacterial Activities

Cancer remains a major global health concern, driving the search for safe and effective bioactive compounds from natural sources. Jujube peel red pigment (JP), an anthocyanin-rich extract, has shown preliminary bioactivity, yet its antitumor potential and delivery challenges remain underexplored. This study systematically evaluated the in vitro antitumor activity of JP and developed a thermosensitive hydrogel-based local delivery system (JP-H) to overcome its rapid diffusion and poor retention. JP exhibited selective cytotoxicity against HeLa cervical cancer and B16 melanoma cells, with no obvious toxicity to normal L929 and RAW264.7 cells. Mechanistically, JP induced mitochondrial-dependent apoptosis via upregulating Bax and cleaved Caspase-9/-3, while downregulating Bcl-2, and concurrently triggered G1/S phase arrest through modulation of CCND1, CDK2, CDK4, PCNA, MYC, and TP53. To enable localized delivery, JP was incorporated into an injectable chitosan/gelatin/F127 thermosensitive hydrogel (JP-H), which exhibited rapid sol-gel transition at physiological temperature, shear-thinning behavior, and a porous microstructure. JP-H not only sustained JP release but also significantly enhanced antibacterial activity against E. coli and S. aureus compared to free JP. Furthermore, JP-H markedly inhibited HeLa cell migration and induced superior apoptotic/necrotic cell death in co-culture assays, outperforming free JP. Collectively, this work establishes JP as a multi-target antitumor agent and demonstrates JP-H as a promising local therapeutic platform combining sustained delivery, antibacterial protection, and enhanced anticancer efficacy for cervical cancer treatment.