Pharmacological treatments of diabetic ulcers remain a huge challenge due to the impaired angiogenesis and uncontrolled bacterial infection. Here, iminopyrazine-based Fe-covalent organic frameworks (Fe-COF) were synthesized via a subcomponent assembly strategy, and functionalized through covalent modification of L-arginine and encapsulated with photosensitizer IR780 and hyaluronic acid for enhancing diabetic wound healing. The functionalized Fe-COF (Fe-COF NRs) showed peroxidase-like activity and near-infrared (NIR)-controlled NO generation property, which can be used for synergistic photothermal/photodynamic antibacterial therapy and NO-based gas therapy. Treatment with Fe-COF NRs + NIR caused pathogenic elimination and enhanced angiogenesis, subsequently leading to accelerated wound healing in a rat model of infected diabetic wound. Mechanistically, the results from RNA sequencing analysis indicated that Fe-COF NRs treatment significantly induced the expression of genes involved in angiogenesis, but obviously inhibited the expression of proinflammatory cytokines. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that collagen-containing extracellular matrix, hair follicle development, PI3K-Akt signaling pathway, wound healing and skin development were significantly enriched after Fe-COF NRs treatment. Taken together, Fe-COF NRs provide a novel therapeutic strategy for the treatment of infected diabetic wound.
Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT-based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near-infrared fluorescence imaging (NIRFI) imaging-guided photo-induced triple-therapy for cancer. Thermosensitive liposomes co-loaded with SPIONs/IR780 and Abemaciclib (SIA-TSLs), peptide ACKFRGD, and click group 2-cyano-6-amino-benzothiazole (CABT) are co-modified on the surface of SIA-TSLs to form SIA- α TSLs. ACKFRGD can be hydrolyzed to expose the 1, 2-thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA- α TSLs aggregates. The aggregation of SIA- α TSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo-induced triple-therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA- α TSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM-CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy.
危险品化学品经营许可证（带存储）