Targeted Delivery of Apoptotic Cell‐Derived Nanovesicles prevents Cardiac Remodeling and Attenuates Cardiac Function Exacerbation

Abstract

The modulation of inflammatory responses plays an important role in the pathobiology of cardiac failure. In a natural healing process, the ingestion of apoptotic cells and their apoptotic bodies by macrophages in a focal lesion result in resolution of inflammation and regeneration. However, therapeutic strategies to enhance this natural healing process using apoptotic cell‐derived biomaterials have not yet been established. In this study, apoptotic bodies‐mimetic nanovesicles derived from apoptotic fibroblasts (ApoNVs) conjugated with dextran and ischemic cardiac homing peptide (CHP) (ApoNV‐DCs) for ischemia‐reperfusion (IR)‐injured heart treatment are developed. Intravenously injected ApoNV‐DCs actively targeted the ischemic myocardium via conjugation with CHP, and are selectively phagocytosed by macrophages in an infarcted myocardium via conjugation with dextran. ApoNV‐DCs polarized macrophages from the M1 to M2 phenotype, resulting in the attenuation of inflammation. Four weeks after injection, ApoNV‐DCs attenuated cardiac remodeling, preserved blood vessels, and prevented cardiac function exacerbation in IR‐injured hearts. Taken together, the findings may open a new avenue for immunomodulation using targeted delivery of anti‐inflammatory nanovesicles that can be universally applied for various inflammatory diseases.

Progress of cell membrane-derived biomimetic nanovesicles for cancer phototherapy

“…39 Nanovesicles derived from cell membrane are now widely acknowledged as key nanovehicles that regulate the biological activity of multicellular animals in an intercellulartransmission way. 40,41 They are crucial for regulating many physiological functions, including the survival of stem cells, 42 tissue regeneration 41,43 and immunological control, 44 as well as the pathogenesis that underlies the development of many diseases. 45 We now have a much better grasp of cell membrane-derived biomimetic nanovesicle nanotechnology.…”

“…23 Additionally, they possess inherent biophysical and biochemical features for activating a particular single/chain physiological behavior for the therapy of various diseases through their fascinating endogenous capabilities, such as precise target-homing selectivity and immunosurveillance. 41,47 Nanovesicles are thus determined to be a natural nanocarrier with much better biocompatibility and bioavailability than traditional synthetic nanomedicine from a materials perspective, as the cell-derived hierarchical nanoarchitectures of nanovesicle-based biomimetic nanomedicine represent an evolving type of nanocarrier, mounted with a responsive molecule-decorated phospholipid bilayer and an enclosed parental matrix in the same topological configuration. 7,48,49 Therefore, it is proposed here that the main concepts for creating cell membranederived biomimetic nanovesicles can be derived from conventional synthetic nanomedicines.…”