Preclinical evaluation of Targeted IL-1β Knockdown via CD44-Immunoliposomes: A Nano-therapy against the Inflammatory Microenvironment

Chronic inflammation, characterized by the infiltration of macrophages and the heightened release of pro-inflammatory cytokines, is the underlying cause of the pathogenesis of many critical diseases. Therapeutic interventions for controlling inflammation via gene knockdown of inflammatory mediators have emerged as a promising approach for regulating uncontrolled inflammation. This study explores the potential of siIL-1β-anti-CD44-Liposomes (SIL) as a potent anti-inflammatory therapy against pro-inflammatory RAW264.7 macrophages via gene specific knockdown of IL-1β mRNA through RNAi, and the subsequent down-regulation of the pro-inflammatory cytokine loop. The designed SIL exhibited a uniform size of 131.1 ± 0.5 nm with a quasi-spherical morphology and sustained release of siIL-1β within 24 hours. The reduction in pro-inflammatory cytokines like IL-1β, TNF-α, and IL-6 and inflammatory enzymes iNOS and COX-2; and the simultaneous increase in the anti-inflammatory cytokine IL-4, is indicative of the formulation’s therapeutic efficacy in reducing inflammation at a cellular level. The effects of SIL on the Macrophage-T cell crosstalk also uncovers the liposome’s efficacy in reducing cytokine-mediated T cell effector functions. The nuanced effects of siIL-1β-anti-CD44-Liposomes on in-vivo model of chronic inflammation underscore their potential for precise therapeutic interventions in inflammatory conditions, with multifaceted anti-inflammatory effects on tissue levels and cytokine levels.