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

Abstract 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.