A Smart Silk‐Based Microneedle for Cancer Stem Cell Synergistic Immunity/Hydrogen Therapy

Cancer stem cells (CSCs) are responsible for the melanoma recurrence, progression, and ineffective therapy. Despite striking anti-CSCs results in immunotherapy with anti-programmed death-1 antibodies (aPD-1), the therapeutic efficacy is restricted by the evolution of immune evasion of CSCs. Here, a wearable silk-based microneedle device (SMND) integrating a synergistic immunity and hydrogen therapy is developed. The device mainly consists of a double-layered MN patch (DLMNP), which employs aPD-1 loaded silk fibroin (SF) as the inner matrix for immunotherapy, while ammonia borane-loaded mesoporous silica nanoparticles (AB-MSN) encapsulated polycaprolactone as the outer thermal-responsive coating for H-2 releasing. SMND can realize thermally responsive drug release triggered by a smartphone for a sustained anti-CSCs therapy. In B16F10-CSCs bearing mice melanoma models, the results demonstrates that the synergistic treatment strategy can realize a satisfying antitumor and anti-CSCs efficacy, which is accompanied by a minimized systemic toxicity. In summary, the smart and synergistic anti-CSCs features endow SMND as a highly functional platform, which can be potentially extended to chronic disease therapy.