{
  "abstract": "Background Small cell lung cancer (SCLC) characterized by its invasive and infiltrative growth, presents significant challenges for clinical therapy. Proteolysis Targeting Chimera (PROTAC) shows promise in SCLC therapy by diminishing targeted proteins traditionally resistant to small molecular inhibitors. Yet, their effectiveness is limited by the tumor resistance and lack of tumor specificity.Methods We innovatively engineered a double-layered microneedle (MN) patch by integrating acid and ROS dual-activatable PROTAC nanoparticles and self-oxygenating BSA-MnO 2 nanoparticles into one nanoplatform to overcome the tumor resistance. The microneedle patch were administrated locally at the tumor site to penetrate the tumor and enhance photodynamic therapy (PDT), thus precisely induced bromodomain and extraterminal protein 4 (BRD4) degradation for effective tumor eradication.Results Upon administration, the outer layer of the microneedle swiftly releases the PROTAC nanoparticles quickly, which can be specifically activated in the intracellular acidic environment of tumor cells for performing PDT and restored PROTAC prodrug for precise BRD4 degradation. Simultaneously, the BSA-MnO 2 nanoparticles loaded inside the inner layer of the MNs acted as an oxygen supply station to counteract tumor hypoxia, and thus promoted PDT and PROTAC activation. This PROTAC-delivered MNs significantly inhibited tumor growth in both subcutaneous and orthotopic SCLC tumor models.Conclusions Self-oxygenating PROTAC MNs successfully circumvented the tumor tissue, inducing enhanced BRD4 degradation and PDT for SCLC treatment ( figure 1). This multifunctional MNs might provide a robust nanoplatform for precise protein degradation and highly efficient SCLC therapy.Abstract 188 Figure 1Graphic abstract",
  "authors": [
    {
      "affiliations": [
        "Shanghai, Hong Kong"
      ],
      "name": "Meng Hou"
    }
  ],
  "title": "188 Self-oxygenating PROTAC microneedles for spatiotemporally-tunable protein degradation and enhanced small cell lung cancer therapy",
  "uid": "032c6889-4e2b-52ab-83d9-d83dba87a7d7"
}