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

## TL;DR

Researchers created a new liposome that targets inflamed lungs to reduce inflammation and improve recovery in acute lung injury.

## Contribution

A novel CCR2-overexpressed liposome was developed to enhance CEP delivery and targeting in acute lung injury.

## Key findings

- CEP@LP-MCCR2 showed increased lung accumulation and cellular uptake compared to free CEP.
- The liposome reduced pro-inflammatory cytokines and suppressed M1 macrophage polarization.
- RNA sequencing suggested inactivation of the TNF/NF-κB signaling pathway by CEP@LP-MCCR2.

## Abstract

What are the main findings?
We developed CEP@LP-MCCR2; the original liposome integrates the advantages of cell membranes and lipid materials.CEP@LP-MCCR2 enables efficient accumulation of CEP in inflamed lungs.CEP@LP-MCCR2 is equipped with a CCR2-overexpressed surface, enabling it to selectively combine CCL2, which is related to acute lung injury (ALI).CEP@LP-MCCR2 could reduce the levels of key pro-inflammatory cytokines, suppress M1 macrophage polarization, and upregulate the expression of junctional proteins.RNA sequencing indicated that CEP@LP-MCCR2 may inactivate the TNF/NF-κB signaling axis.

We developed CEP@LP-MCCR2; the original liposome integrates the advantages of cell membranes and lipid materials.

CEP@LP-MCCR2 enables efficient accumulation of CEP in inflamed lungs.

CEP@LP-MCCR2 is equipped with a CCR2-overexpressed surface, enabling it to selectively combine CCL2, which is related to acute lung injury (ALI).

CEP@LP-MCCR2 could reduce the levels of key pro-inflammatory cytokines, suppress M1 macrophage polarization, and upregulate the expression of junctional proteins.

RNA sequencing indicated that CEP@LP-MCCR2 may inactivate the TNF/NF-κB signaling axis.

What are the implications of the main findings?
CEP@LP-MCCR2 mitigates the limitations of free CEP, namely, its poor solubility and inferior biocompatibility.CEP@LP-MCCR2 has the potential to reduce inflammation and recovery barrier function, which could attenuate of ALI.CEP@LP-MCCR2 offers novel potential targeting.

CEP@LP-MCCR2 mitigates the limitations of free CEP, namely, its poor solubility and inferior biocompatibility.

CEP@LP-MCCR2 has the potential to reduce inflammation and recovery barrier function, which could attenuate of ALI.

CEP@LP-MCCR2 offers novel potential targeting.

Severe respiratory inflammation or viral infections can lead to acute lung injury (ALI), a disease characterized by diffuse inflammatory injury of the pulmonary epithelium and endothelium. Cepharanthine (CEP) is reported as a promising drug candidate due to its antiviral properties. However, CEP exhibits poor solubility and low bioavailability. Therefore, we developed a novel liposome, named CEP@LP-MCCR2, which integrates the advantages of cell membranes and lipid materials, to achieve effective accumulation of CEP in inflamed lungs. It exhibits a 1.73-fold increase in lung accumulation at 24 h in vivo, a 4.56-fold increase in cellular uptake in MLE-12 cells. CEP@LP-MCCR2 is equipped with a CCR2-overexpressed surface, enabling it to selectively neutralize elevated levels of CCL2, which is related to ALI, thereby reducing macrophage infiltration, thereby reducing the spread of inflammation, such as a reduction in levels of key pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). CEP@LP-MCCR2 could suppress M1 macrophage polarization, which led to a marked decrease in iNOS and an increase in Arg1. It upregulated the expression of junctional proteins E-cadherin and Occludin, indicating potential recovery of the pulmonary epithelial barrier. RNA sequencing analysis implied the potential of CEP@LP-MCCR2 to inactivate the TNF/NF-κB signaling axis.