RESUMO
Activated fibroblast-like synovial (FLS) cells are regarded as an important target for rheumatoid arthritis (RA) treatment via starvation therapy mediated by glucose oxidase (GOx). However, the hypoxic RA-FLS environment greatly reduces the oxidation process of glucose and leads to a poor therapeutic effect of the GOx-based starvation therapy. In this work, we designed a hollow mesoporous copper sulfide nanoparticles (CuS NPs)-based smart GOx/atovaquone (ATO) codelivery system (named as V-HAGC) targeting RA-FLS cells to realize a O2-economized dual energy inhibition strategy to solve the limitation of GOx-based starvation therapy. V-HAGC armed with dual multi-stimuli-responsive "doorkeepers" can guard drugs intelligently. Once under the stimulation of photothermal and acidic conditions at the targeted area, the dual intelligent responsive "doors" would orderly open to realize the controllable release of drugs. Besides, the efficacy of V-HAGC would be much improved by the additional chemodynamic therapy (CDT) and photothermal therapy (PTT) stimulated by CuS NPs. Meanwhile, the upregulated H2O2 and acid levels by starvation therapy would promote the Fenton-like reaction of CuS NPs under O2-economized dual energy inhibition, which could enhance the PTT and CDT efficacy as well. In vitro and in vivo evaluations revealed V-HAGC with much improved efficacy of this combination therapy for RA. In general, the smart V-HAGC based on the O2-economized dual energy inhibition strategy combined with enhanced CDT and PTT has the potential to be an alternative methodology in the treatment of RA.
Assuntos
Artrite Reumatoide , Nanopartículas , Neoplasias , Humanos , Cobre/farmacologia , Cobre/uso terapêutico , Terapia Fototérmica , Glucose Oxidase/uso terapêutico , Atovaquona/uso terapêutico , Peróxido de Hidrogênio , Nanopartículas/uso terapêutico , Sulfetos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucose , Nanotecnologia , Neoplasias/tratamento farmacológico , Linhagem Celular TumoralRESUMO
The incidence of inverted knee osteoarthritis is slowly increasing, there are technical limitations in the treatment, and the operation is difficult. In this article, we will study the benefits and costs of arthroscopic cleaning treatments based on intelligent electronic medicine. This article focuses on knee osteoarthritis patients in the EL database. There are 12 male patients, accounting for 66.67%, and 6 female patients, accounting for 33.33%. The average body mass index (BMI) of the patients was 28.08, the average time from first knee discomfort to surgery was 28.44 months, and the average time of arthroscopic debridement treatment for patients with VKOH knee osteoarthritis was 143.11 minutes. One case of perioperative complication occurred within 35 days after operation, which was a soleus muscle intermuscular venous thrombosis. After immobilization and enhanced anticoagulation for 1 week, it was stable without risk of shedding. The average postoperative study time was 20.00 months. The electronic medical arthroscopy cleaning treatment plan in this article can greatly improve the quality of life of patients and can check the pathological state in time, with low cost. In the course of treatment, comprehensive treatment costs can be saved by 45%. Arthroscopic clean-up treatment can not only reduce knee pain and other uncomfortable symptoms, restore normal knee joint function, and improve the quality of life of patients, but also correct the unequal length of the lower limbs, thereby avoiding spinal degeneration caused by knee instability. Therefore, it is the first choice for the treatment of advanced knee osteoarthritis in patients with VKOH.