ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.
ABSTRACT
@#Mesoporous silica nanoparticle as drug carrier has become the new research focus in the field of nano-drug delivery system in recent years. In this study, paclitaxel-loaded msesoporous silica nanoparticle(PTX@MSN)was manufactured by the solvent adsorption. In vitro studies revealed that PTX@MSN was well dispersed in aqueous medium with particle size of 250 nm, the potential of -(8. 01±1. 81)mV and drug loading efficiency of(23. 76±1. 14)%. PTX@MSN showed the sustained-release characteristics with the cumulative PTX of release(23. 62±2. 15)% at 24 h. In additions, the cytotoxicity investigation indicated that blank MSNs were biocompatible while PTX@MSN group showed improved in vitro anti-tumor activity against HepG2 cell when compared with Taxol group. In conclusion, MSN is a promising platform to build drug delivery systems for tumor therapy.
ABSTRACT
To study the multidrug resistance activity of 1-alkyl-2-acetyl-1, 2, 3, 4-tetrahydroisoquinoline derivatives. Methods: A series of novel tetrahydroisoquinoline derivatives bearing at C-1 position a carbon chain derived from fatty acids were prepared through the Bischler-Napieralski cyclization reaction. Their multidrug resistance (MDR) reversal cancerous multidrug resistance activities were evaluated against K562 and K562/DOX cell lines in vitro by MTT assay with verapamil as a control. Results and Conclusion: The structures of these tetrahydroisoquinolines were confirmed by extensive spectroscopic methods(1H NMR, MS, IR and elemental ana-lyses). MDR results showed that compounds 7 and 10 exhibited moderate reversal activities, and were slightly less potent than those of verapamil against K562 cell line. It is believed that compounds 7 and 10 have MDR activity.