Juxtamembrane Mimic Peptide Loaded Injectable Sodium Alginate/Bioglass Bioactive Hydrogel for Suppressing Tumor Recurrence in Post-Breast-Conserving-Surgery Treatment

Breast cancer remains the most diagnosed tumor among women worldwide, and tumor recurrence following breast-conserving surgery presents a major clinical challenge. To address this, we developed a functional injectable sodium alginate/bioactive glass (SA/BG) hydrogel loaded with a juxtamembrane-2 (JM2) mimic peptide (JM2@SA/BG) for breast tumor postsurgical treatment. The hydrogel exhibited rapid in situ gelation, tunable swelling, and mechanical strength well-matched to natural breast tissue, with JM2 incorporation increasing crosslinking density through ionic and hydrogen bonding. A sustained, diffusion-controlled release of JM2 was achieved by encapsulating JM2 into the SA/BG hydrogel, which was consistent with the Higuchi model, ensuring prolonged therapeutic bioavailability. In vitro, JM2 exhibited a selective inhibition on 4T1 breast cancer cells (IC50 = 65 μg/mL) while maintaining high biocompatibility with fibroblasts. In vivo, with a murine breast cancer postsurgery model, the JM2@SA/BG hydrogel significantly suppressed tumor recurrence, evidenced by the reduced Ki67-positive proliferating cells, increased TUNEL-positive apoptotic cells, and nuclear abnormalities in the remaining tumor tissue demonstrated by H&E staining. Collectively, these results highlight the JM2@SA/BG hydrogel as a promising injectable and functional platform that provides spatiotemporal control of drug delivery, possesses localized anticancer activity, and offers an effective strategy to suppress tumor recurrence in breast cancer postsurgery therapy.