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The limited therapeutic strategies available for stroke leave many patients disabled for life. This study assessed the potential of programmed death‐ligand 1 (PD‐L1) and hepatocyte growth factor (HGF)‐engineered mesenchymal stem cell‐derived exosomes (EXO‐PD‐L1‐HGF) in enhancing neurological recovery post‐stroke. EXO‐PD‐L1‐HGF, which efficiently endocytosed into target cells, significantly diminishes the H2O2‐induced neurotoxicity and increased the antiapoptotic proteins in vitro. EXO‐PD‐L1‐HGF attenuates inflammation by inhibiting T‐cell proliferation and increasing the number of CD8+CD122+IL‐10+ regulatory T cells. Intravenous injection of EXO‐PD‐L1‐HGF could target stromal cell‐derived factor‐1α (SDF‐1α+) cells over the peri‐infarcted area of the ischemic brain through CXCR4 upregulation and accumulation in neuroglial cells post‐stroke. EXO‐PD‐L1‐HGF facilitates endogenous nestin+ neural progenitor cell (NPC)‐induced neurogenesis via STAT3‐FOXO3 signaling cascade, which plays a pivotal role in cell survival and neuroprotection, thereby mitigating infarct size and enhancing neurological recovery in a murine stroke model. Moreover, increasing populations of the immune‐regulatory CD19+IL‐10+ and CD8+CD122+IL‐10+ cells, together with reducing populations of proinflammatory cells, created an anti‐inflammatory microenvironment in the ischemic brain. Thus, innovative approaches employing EXO‐PD‐L1‐HGF intervention, which targets SDF‐1α+ expression, modulates the immune system, and enhances the activation of resident nestin+ NPCs, might significantly alter the brain microenvironment and create a niche conducive to inducing neuroplastic regeneration post‐stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The biocompatible thiol-functionalized rGOSH/PMASH microcapsules encapsulating nerve growth factor (NGF) are arrayed onto a transparent and conductive substrate, i.e., indium tin oxide (ITO), to integrate electrically stimulated cellular differentiation, electrically controlled NGF release, and topographically rough nano-surfaces into a 3-D platform for nerve regeneration. The rGOSH/PMASH microcapsules with microscale topography function not only as an adhesive coating to promote the adhesion of PC12 cells but also as electroactive NGF-releasing electrodes that stimulate NGF release and accelerate the differentiation of PC12 cells during electrical stimulation. Once electrical treatment is applied, NGF release and electrically enhanced cellular differentiation lead to an obvious increase both in the percentage of cells with neurites and in the neurite length. This length can reach nearly 90 μm within 2 days of cell culture. The average neurite length is significantly increased (four-fold) after culture on the rGOSH/PMASH microcapsule substrate for 2 days compared with culture on a substrate without an rGOSH/PMASH coating. These multifunctional rGOSH/PMASH microcapsules may be used as potential 3-D patterned substrates for neural regeneration and neural prosthetics in tissue engineering applications. [ABSTRACT FROM AUTHOR]