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Glutathione-Responsive Metal-Organic-Framework-Derived MnO/(A/R)TiO Nanoparticles for Enhanced Synergistic Sonodynamic/Chemodynamic/Immunotherapy.

ACS Nano

January 2025

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.

Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal-organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnO/(A/R)TiO (MTO) in situ from MIL-125-NH (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation.

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Background: Biosimilar natalizumab (biosim-NTZ) is the first biosimilar monoclonal antibody of reference natalizumab (ref-NTZ) for treatment of relapsing forms of multiple sclerosis (MS). Within the totality of evidence for demonstration of biosimilarity, immunogenicity assessments were performed in healthy subjects and patients with relapsing-remitting MS (RRMS) to confirm a matching immunogenicity profile between biosim-NTZ and ref-NTZ.

Methods: Immunogenicity of biosim-NTZ versus ref-NTZ was evaluated in two pivotal clinical studies.

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Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung.

Nat Commun

January 2025

Center for Infection and Immunity, Guangdong Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.

Suppression of chimeric antigen receptor-modified T (CAR-T) cells by the immunosuppressive tumor microenvironment remains a major barrier to their efficacy against solid tumors. To address this, we develop an anti-PD-L1-expressing nanovesicle loaded with the STING agonist cGAMP (aPD-L1 NVs@cGAMP) to remodel the tumor microenvironment and thereby enhance CAR-T cell activity. Following pulmonary delivery, the nanovesicles rapidly accumulate in the lung and selectively deliver STING agonists to PD-L1-overexpressing cells via the PD-1/PD-L1 interaction.

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Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).

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Background: Corneal squamous cell carcinoma (cSCC) is a rare neoplasm of dogs that can be treated with various modalities, principally by superficial keratectomy (SK) surgery. It is common to treat cSCC with multiple adjunctive therapies, but this may not always be practical for clinicians, clients, or patients.

Aim: This retrospective study describes the signalment of affected dogs, concurrent medical therapy, and success rate of surgical treatment of cSCC with SK surgery alone or in combination with adjunct therapy.

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