RESUMEN
Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.
RESUMEN
Implantable electrodes have raised great interest over the last years with the increasing incidence of neurodegenerative disorders. For brain implant devices, some key factors resulting in the formation of glial scars, such as mechanical mismatch and acute injury-induced inflammation, should be considered for material design. Therefore, in this study, a new biocompatible flexible electrode (e-SgG) with arbitrary shapes on a positive electrode was developed via electrogelation by applying a direct electrical voltage on a silk fibroin/gelatin/reduced graphene oxide composite hydrogel. The implantable flexible e-SgG-2 film with 1.23% rGO content showed high Young's modulus (11-150 MPa), which was sufficient for penetration under dried conditions but subsequently became a biomimetic brain tissue with low Young's modulus (50-3200 kPa) after insertion in the brain. At the same time, an anti-inflammatory drug (DEX) incorporated into the e-SgG-2 film can be electrically stimulated to exhibit two-stage release to overcome tissue inflammation during cyclic voltammetry via degradation by applying an AC field. The results of cell response to the SF/gelatin/rGO/DEX composite film showed that the released DEX could interrupt astrocyte growth to reduce the inflammatory response but showed non-toxicity toward neurons, which demonstrated a great potential for the application of the biocompatible and degradable e-SgG-D electrodes in the improvement of nerve tissue repair.
