Affiliation:
1. Department of Cardiovascular Medicine Heart Failure Center Ruijin Hospital, and Ruijin Hospital Lu Wan Branch Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road, 149 S. Chongqing Road Shanghai 200023 China
2. Institute of Cardiovascular Diseases Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200023 China
3. Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200023 China
Abstract
AbstractThe lesion core is the area with the most serious injury and vigorous repair. Existing nanocarriers are difficult to break through the targeted delivery to the lesion core for precise treatment in the intracellular and extracellular microenvironment. Herein, a cellular membrane‐engineered nanovesicle (CMEV) with a hierarchical structure is constructed using the double emulsion‐extrusion method by integrating a neutrophil membrane, functional antibody, and gelled drug‐loaded core as a three‐stage booster to target the lesion core and deliver catestatin (CST), a small therapeutic peptide, for ischemic cardiomyopathy therapy. By coating the neutrophil membrane outside the shell, CMEV is endowed with the function of neutrophil‐like migration to achieve the first stage of tissue targeting. Based on the specific anchoring to injured myocardium, a myosin light chain 3 (MLC3) antibody is embedded to fulfill the second stage of CMEV accumulation in the lesion core. The gelled core containing CST‐sodium alginate (NaAlg) with a pH‐responsive shell is prepared by ionic cross‐linking to accomplish the third stage of precise CST administration. Triggered by the microenvironment, NaAlg electrostatically adheres to the lesion core for sustained release, enhancing the efficacy of CST in improving cardiomyocyte apoptosis, excessive fibrosis, macrophage polarization, and angiogenesis. Thus, the “three‐stage booster” nanovesicle significantly ameliorates cardiac function and adverse remodeling to treat ischemic cardiomyopathy.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Program of Shanghai Academic Research Leader
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science