Antioxidant Response Activating nanoParticles (ARAPas) localize to atherosclerotic plaque and locally activate the Nrf2 pathway

Abstract

Atherosclerotic disease is the leading cause of death world-wide with few novel therapies available despite the ongoing health burden. Redox dysfunction is a well-established driver of atherosclerotic progression; however, the...

Advances in Nrf2 Signaling Pathway by Targeted Nanostructured-Based Drug Delivery Systems

“…CDDO-Me is undergoing a Phase I trial in cancer patients [63]. To this end, in a most recent study, encapsulation of an Nrf2 activator, CDDO-methyl into polymeric nanoparticles, led to the upregulation of the expression of antioxidants and cytoprotective proteins for atheroprotection [64]. They showed the accumulation of nanoparticles in atherosclerotic plaque of ApoE −/− and LDLr −/− mice, which were accompanied by the activation of Nrf2.…”

The Use of Acute Immunosuppressive Therapy to Improve Antibiotic Efficacy against Intracellular Staphylococcus aureus

“…Nrf2 is a transcription factor that drives expression of antioxidants and anti-inflammatory cytokines during the resolution phase of the immune response ( 13 , 14 ). Increased Nrf2 signaling has been shown to attenuate the NF-κB inflammatory response and decrease iNOS expression and ROS production in macrophages ( 13 – 15 ).…”

“…As Nrf2 signaling leads to decreased ROS levels, we hypothesized that activation of Nrf2 signaling would increase antibiotic susceptibility of S. aureus in macrophages. To test this, we employed two Nrf2 activators: sulforaphane ( 17 ) and CDDO-methyl (CDDOMe; also called bardoxolone methyl) encapsulated in Antioxidant Response Activating nanoParticles (ARAPas) ( 15 ) CDDOMe ARAPas were recently shown to target to macrophages and block inflammatory signaling ( 15 ) To determine if Nrf2 signaling increases antibiotic susceptibility of S. aureus , BMDMs were treated with either sulforaphane ( Fig. 2A to C ) or CDDOMe ARAPas ( Fig.…”

“…After 7 days, cells were plated at 4 × 10 5 cells/mL in minimum essential media (MEM) + 10% FBS + l -glutamine (complete MEM) and allowed to adhere overnight at 37°C, 5% CO 2 . BMDMs were treated with 10 μM sulforaphane ( 17 ), 400 nM CDDOMe ARAPas ( 15 ), 100 nM dexamethasone ( 30 ), or 10 μM rosiglitazone ( 9 ) overnight. BMDMs were incubated with S. aureus strain LAC at MOI 10 for 45 min at 37°C, 5% CO 2 to allow for internalization.…”