Implanted Microneedles Loaded with Sparfloxacin and Zinc-Manganese Sulfide Nanoparticles Activates Immunity for Postoperative Triple-Negative Breast Cancer to Prevent Recurrence and Metastasis.

Abstract

Recent investigations have underscored the significant role of manganese ions (Mn²⁺) in immunization, particularly through the activation of the cGAS-STING pathway, which enhances antitumor immune responses. However, the rapid metabolism of free Mn²⁺ following administration limits its effectiveness as an immune adjuvant. To address these challenges, microneedles (MNs) of hyaluronic acid containing Sparfloxacin (SP) and zinc-manganese sulfide (ZMS) are prepared for the postoperative in situ treatment of triple-negative breast cancer (TNBC) to prevent cancer recurrence and combat wound infection. ZMS/SP (ZS)-loaded MNs exhibit strong antimicrobial and antibiofilm properties that are crucial for preventing postoperative infections. Moreover, the generation of reactive oxygen species by these MNs disrupts the oxidative balance, effectively activating immunogenic cell death and facilitating the release of cytokines. ZS significantly suppressed tumor growth, reduced lung metastasis, and promoted wound healing. These effects are accompanied by notable increases in immune cell infiltration and activation, which is consistent with the gene sequencing results. Activation of the cGAS-STING pathway further improved antitumor immunity. These findings highlight the potential of ZS MNs as an effective and safe treatment that utilizes the immunostimulatory properties of Mn²⁺ to enhance local and systemic immune responses for the prevention of postoperative TNBC metastasis.