Engineered CCR2 Cell Membrane-Wrapped Cepharanthine Liposomes for Potential Targeted Attenuation of Acute Lung Injury

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Pulmonary Medicine

Background:

• Acute lung injury (ALI) involves severe respiratory inflammation and viral infections, damaging lung epithelium and endothelium.
• Cepharanthine (CEP) shows antiviral potential but suffers from poor solubility and bioavailability.
• Current treatments for ALI lack targeted delivery and efficacy.

Purpose of the Study:

• To develop a novel liposomal formulation of cepharanthine (CEP@LP-M^CCR2) for enhanced lung accumulation and targeted delivery.
• To investigate the therapeutic efficacy of CEP@LP-M^CCR2 in reducing inflammation and restoring pulmonary function in ALI models.
• To explore the underlying molecular mechanisms of CEP@LP-M^CCR2 in mitigating ALI.

Main Methods:

• Development of a novel liposome (CEP@LP-M^CCR2) integrating cell membranes and lipid materials with CCR2-overexpressed surface.
• In vivo assessment of lung accumulation and cellular uptake studies in MLE-12 cells.
• Analysis of inflammatory cytokine levels, macrophage polarization (M1/M2), and pulmonary epithelial barrier protein expression.
• RNA sequencing to elucidate the effect on signaling pathways like TNF/NF-κB.

Main Results:

• CEP@LP-M^CCR2 demonstrated a 1.73-fold increase in lung accumulation and a 4.56-fold increase in cellular uptake.
• Selective neutralization of CCL2 by CEP@LP-M^CCR2 reduced macrophage infiltration and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).
• CEP@LP-M^CCR2 suppressed M1 macrophage polarization, increased epithelial junctional proteins (E-cadherin, Occludin), and potentially inactivated the TNF/NF-κB axis.

Conclusions:

• CEP@LP-M^CCR2 effectively targets inflamed lungs, improving cepharanthine delivery and bioavailability.
• The formulation shows significant potential in mitigating ALI by reducing inflammation, modulating macrophage response, and restoring epithelial barrier integrity.
• CEP@LP-M^CCR2 represents a promising therapeutic strategy for acute lung injury, warranting further clinical investigation.