Chenglong Li, Yan Li, Qing Zeng, Yang Zhou, Huaiyu Su, Yangyun Han, Chen Li
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引用次数: 0
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.
期刊介绍:
Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs.
Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.