Bismuth-based dissolvable microneedle: A precision-targeted "surgical scalpel" for dual-gas synergistic tumor therapy

Breast cancer remains the leading cause of cancer-related deaths because conventional therapies are constrained by systemic toxicity, insufficient specificity, and low patient adherence to patients. In this study, we developed a dissolvable microneedle (MN) platform integrating Bi/Bi₂SiO₅@SiO_2-x nanocomposites with gaseous prodrugs L-arginine (L-Arg) and ammonia borane (AB) for imaging-guided synergistic therapy. Bi-based nanocomposites exhibit strong near-infrared (NIR) absorption, efficient singlet oxygen (¹O₂) generation, and high X-ray attenuation, enabling effective tumor ablation and real-time computed tomography (CT) imaging. An appropriately designed SiO_2-x shell not only protects Bi from oxidation and prevents performance degradation but also efficiently captures the energy transferred from Bi, further facilitating ¹O₂ generation. The L-Arg and AB incorporated into the dissolvable MNs achieved a pH-responsive release of NO and H₂ following transdermal absorption, thereby enhancing photothermal, photodynamic, sonodynamic, and dual-gas synergistic therapies under NIR and ultrasound stimulation. In vitro and in vivo experiments confirmed its potent antitumor efficacy, outstanding biocompatibility, and minimal invasiveness. This study introduces a multifunctional therapeutic platform that addresses the key limitations of breast cancer therapy, offering a precise and non-invasive treatment strategy.