A carrier-free nano-drug assembled via π-π stacking interaction for the treatment of osteoarthritis.

Osteoarthritis (OA) is considered to be the most common joint disorder. Exogenous drug intervention is one of the effective means for OA treatment. Clinical applications of numerous drugs are restricted owing to the short retention as well as rapid clearance in the joint cavity. A wide variety of carrier-based nanodrugs have been developed, but additional carriers may bring unexpected side effects or even toxicity. Herein, by exploiting the spontaneous fluorescence of Curcumin, we designed a new carrier-free self-assembly nanomedicine Curcumin (Cur)/icariin (ICA) nanoparticles with adjustable particle size, which is composed of two small-molecule natural drugs assembled via π-π stacking interaction. Experimental results revealed that Cur/ICA NPs endowed with little cytotoxicity, high cellular uptake and sustained drug release, could inhibit secretion of inflammatory cytokines and reduce cartilage degeneration. Moreover, both the in vitro and in vivo experiments showed the NPs exerted superior synergism effects in anti-inflammatory and cartilage protection than either Cur or ICA alone, and self-monitored its retention by autofluorescence. Thus, the new self-assembly nano-drug combining Cur and ICA represents a new strategy for the treatment of osteoarthritis.

Promising targets and drugs in rheumatoid arthritis: a module-based and cumulatively scoring approach.

AIMS: Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. METHODS: We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. RESULTS: Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. CONCLUSION: This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening.Cite this article: Bone Joint Res 2020;9(8):501-514.