Metal-Organic Framework PCN-224 Combined Cobalt Oxide Nanoparticles for Hypoxia Relief and Synergistic Photodynamic/Chemodynamic Therapy.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.

Efficacy of non-conventional synthetic DMARDs for patients with rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). METHODS: PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI. RESULTS: A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV1 and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=-4.62, 95% CI -8.90 to -0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively. CONCLUSION: ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD. PROSPERO REGISTRATION NUMBER: CRD42022356816.

Nanoscale Metal-Organic Frameworks Combined with Metal Nanoparticles and Metal Oxide/Peroxide to Relieve Tumor Hypoxia for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is a clinically approved noninvasive tumor therapy that can selectively kill malignant tumor cells, with promising use in the treatment of various cancers. PDT is typically composed of three important parts: the specific wavelength of light, photosensitizer (PS), and oxygen. With the progressing investigation on PDT treatment, the most recent attention has focused on improving photodynamic efficiency. Tumor hypoxia has always been a critical factor hindering the efficacy of PDT. Nanoscale metal-organic frameworks (nMOF), the fourth generation of PS, present great potential in photodynamic therapy. In particular, nMOF combined with metal nanoparticles and metal oxide/peroxide has demonstrated unique properties for enhanced PDT. The metal and metal oxide nanoparticles can catalyze H2O2 to generate oxygen or automatically produces oxygen, alleviating the hypoxia and improving the photodynamic efficiency. Metal peroxide nanoparticles can spontaneously produce oxygen in water or under acidic conditions. Therefore, this Review summarizes the recent development of nMOF combined with metal nanoparticles (platinum nanoparticles and gold nanoparticles) and metal oxide/peroxide (manganese dioxide, ferric oxide, cerium oxide, calcium peroxide, and magnesium peroxide) for enhanced photodynamic therapy by alleviating tumor hypoxia. Finally, future perspectives of nMOF combined nanomaterials in PDT are put forward.