NLRP3 Inflammasome-Targeting Nanomicelles for Preventing Ischemia–Reperfusion-Induced Inflammatory Injury

Abstract

Ischemia−reperfusion (I/R) injury is a disease process that affects several vital organs. There is widespread agreement that the NLRP3 inflammasome pathway plays a crucial role in the development of I/R injury. We have developed transferrinconjugated, pH-responsive nanomicelles for the entrapment of MCC950 drug. These nanomicelles specifically bind to the transferrin receptor 1 (TFR1) expressed on the cells of the blood−brain barrier (BBB) and thus help the cargo to cross the BBB. Furthermore, the therapeutic potential of nanomicelles was assessed using in vitro, in ovo, and in vivo models of I/R injury. Nanomicelles were injected into the common carotid artery (CCA) of a middle cerebral artery occlusion (MCAO) rat model to achieve maximum accretion of nanomicelles into the brain as blood flows toward the brain in the CCA. The current study reveals that the treatment with nanomicelles significantly alleviates the levels of NLRP3 inflammasome biomarkers which were found to be increased in oxygen−glucose deprivation (OGD)-treated SH-SY5Y cells, the I/Rdamaged right vitelline artery (RVA) of chick embryos, and the MCAO rat model. The supplementation with nanomicelles significantly enhanced the overall survival of MCAO rats. Overall, nanomicelles exerted therapeutic effects against I/R injury, which might be due to the suppression of the activation of the NLRP3 inflammasome.

Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing

“…Similarly, for aliphatic C-H stretching, the peak was at 2878 cm −1 in chitosan, 2867 cm −1 , 2950 cm −1 in ECNP, 2826 cm −1 in insulin, and 2878 cm −1 and 2950 cm −1 in ICNP [ 61 ]. The peak indicating C=O stretch (Amide-I, O=C–NHR) was found at 1642 cm −1 in chitosan, ECNP, ICNP, and 1641.99 cm −1 in insulin [ 62 ], while for N–H bend (Amide-II) it appears at 1561 cm −1 for chitosan, 1533.65 cm −1 for insulin and at 1536 cm −1 for both ECNP and ICNP [ 63 ]. In addition to these peaks, a peak at 1431 cm −1 in insulin and 1447 cm −1 in ECNP and ICNP was observed exhibiting the S=O bond [ 44 ].…”

Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke

“…Hypoxia and reoxidation induce NLRP3 activation in BV2 microglia through ROS; this activation is, however, inhibited by the Nrf2/ARE pathway [24]. In cerebral ischemia-reperfusion injury, the NLRP3 inflammasome causes an inflammatory response; increases the levels of C-X-C motif chemokine 1, IL-1, and IL-6; and releases cathepsin B [25]. In this study, NLRP3 correlated positively with memory B cells and activated mast cells and negatively with M2 macrophages and resting dendritic cells.…”

OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine

“…Therefore, extending the residence time in the body through a sustained-release effect is also an key question for calcin to enhance the antagonistic effect on heart diseases. Regarding this, OpiCa1-PEG-PLGA nanomicelles were synthesized in this study based on the most common non-toxic nanocarrier PEG-PLGA polymer [ [63] , [64] , [65] ]. We found that OpiCa1-PEG-PLGA nanomicelles keep almost the same effect as OpiCa1 in antagonizing the lethal acute heart failure induced by epinephrine and caffine, and exhibit good cardiac targeting, self-stability, as well as low toxicity.…”