M2-type macrophage membrane-mediated delivery of Carvedilol nanocomplex for acute liver failure treatment and remodeling inflammatory microenvironment  

作　　者：Mingge Shang Yaohui Zhang Junjie Qian Wenchao Wang Xizhi Yu Jiacheng Huang Lin Zhou Shusen Zheng 

机构地区：[1]Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [2]NHC Key Laboratory of Combined Multi-organ Transplantation,Key Laboratory of Organ Transplantation,Hangzhou 310003,China [3]Key Laboratory of the diagnosis and treatment of organ Transplantation,Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer,Chinese Academy of Medical Sciences(2019RU019),Hangzhou 310003,China [4]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,Hangzhou 310003,China [5]Department of Thyroid Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [6]Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College,Hangzhou 310000,China

出　　处：《Nano Research》2024年第7期6362-6375,共14页纳米研究（英文版）

基　　金：supported by grants from the Research Unit Project of Chinese Academy of Medical Sciences(No.2019-I2M-5-030);the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2022002A);the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H030009).

摘　　要：Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting inflammation.Our group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in ALF.We present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at first.Then Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and accumulation.Sustainably released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization efficiency.This study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.

关 键 词：acute liver failure hepatic drug delivery M2 macrophage-camouflaged nanoplatform inflammatory microenvironment macrophage polarization 

分 类 号：R575.3[医药卫生—消化系统]