Biomimetic MCC950‐loaded cerium‐layered double hydroxide nanoparticles for targeted treatment of Type 1 diabetes in streptozotocin‐induced mice

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BACKGROUND AND PURPOSE: The destruction of β-cells in type 1 diabetes is driven by signalling cascades that ultimately lead to cell apoptosis. Both activation of the NLRP3 inflammasome and excessive generation of reactive oxygen species (ROS) act independently and synergistically to promote β-cell apoptosis and accelerate disease progression. Therapeutic approaches that concurrently inhibit NLRP3 activation and oxidative stress may therefore hold promise for preventing or slowing type 1 diabetes development and/or progression. EXPERIMENTAL APPROACH: This study developed a targeted nanotherapeutic consisting of M2 macrophage membrane-coated, MCC950 (a selective NLRP3 inflammasome inhibitor)-incorporated, BSA-loaded cerium-layered double hydroxide nanoparticles (CLMBM NPs), engineered for targeted delivery to inflamed tissues and controlled, ROS-responsive drug release. KEY RESULTS: CLMBM NPs effectively eliminated intracellular ROS and reduced apoptosis in MIN-6 cells. Macrophage membrane cloaking facilitated immune evasion and targeted accumulation in inflamed pancreatic tissue. In streptozocin (STZ) induced diabetic mice, CLMBM NPs demonstrated pancreas-targeted accumulation and ROS-responsive release of MCC950, enabling precise modulation of local inflammation and significant therapeutic effects on blood glucose homeostasis by down-regulating pro-inflammatory markers such as IL-1β and IL-6. CONCLUSIONS AND IMPLICATIONS: Findings reveal that pancreas-targeted CLMBM NPs exert potent anti-ROS, anti-inflammatory and antiapoptotic effects, highlighting a promising therapeutic avenue for targeted immunomodulation in type 1 diabetes.

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