Molecularly Engineered Macrophage‐Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment

Abstract

Atherosclerosis (AS) is a major contributor to cardiovascular diseases worldwide, and alleviating inflammation is a promising strategy for AS treatment. Here, we report molecularly engineered M2 macrophage‐derived exosomes (M2 Exo) with inflammation‐tropism and anti‐inflammatory capabilities for AS imaging and therapy. M2 Exo are derived from M2 macrophages and further electroporated with FDA‐approved hexyl 5‐aminolevulinate hydrochloride (HAL). After systematic administration, the engineered M2 Exo exhibit excellent inflammation‐tropism and anti‐inflammation effects via the surface‐bonded chemokine receptors and the anti‐inflammatory cytokines released from the anti‐inflammatory M2 macrophages. Moreover, the encapsulated HAL can undergo intrinsic biosynthesis and metabolism of heme to generate anti‐inflammatory carbon monoxide and bilirubin, which further enhance the anti‐inflammation effects and finally alleviate AS. Meanwhile, the intermediate protoporphyrin IX (PpIX) of the heme biosynthesis pathway permits the fluorescence imaging and tracking of AS.

<p>Cancer-Derived Exosomes: Their Role in Cancer Biology and Biomarker Development</p>

“…Certainly, exosomal cargoes are not limited by miRNAs only but also by a lot of other candidate molecules such as proteins, lipids, enzymes, signaling molecules, which can exert their functional activities far from the exosome-producing cells. 84 Table 3 demonstrates that CDE cargoes could contain basically any purpose-built loaded nano-molecules for its ultimately release from the parental cells. It is evident that horizontal or paracrine transfer of these molecules, when received by the specific recipient cells in the TME or any distant metastatic niches, could facilitate the progression, invasion, and metastatic spread of cancer cells.…”

Extracellular vesicle signalling in atherosclerosis

“…Another in vitro study observed that when macrophages and SMC were treated with EC-derived EVs loaded with anti-miR-33a-5p, ATP-binding cassette transporter ABCA1 protein expression was increased and elevated apoAI-mediated cholesterol efflux was observed too [ 222 ]. Molecularly engineered EVs for treatment of atherosclerosis have also been investigated [ 223 ]. Wu et al, exploited M2 macrophage-derived EVs which were electoporated and loaded with the FDA approved compound, hexyl 5-aminolevulinate hydrochloride (HAL) [ 223 ].…”

“…Molecularly engineered EVs for treatment of atherosclerosis have also been investigated [ 223 ]. Wu et al, exploited M2 macrophage-derived EVs which were electoporated and loaded with the FDA approved compound, hexyl 5-aminolevulinate hydrochloride (HAL) [ 223 ]. Administration of engineered EVs to apoE −/− mice under high fat diet showed reduced lesion area compared to control mice or mice receiving HAL or M2-derived EVs.…”

“…Administration of engineered EVs to apoE −/− mice under high fat diet showed reduced lesion area compared to control mice or mice receiving HAL or M2-derived EVs. In vitro experiments revealed that engineered EVs had higher levels of anti-inflammatory cytokines such as IL-10 [ 223 ]. EVs as vectors offer an enormous opportunity for the development of new pharmacological therapies and will be an area of further investigation in the future.…”

Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

“…Exosomes have emerged as an alternative to those exogenous nanoparticles [15,16]. These membraneenclosed vesicles with sizes of 40-150 nm are naturally secreted by various cell types, which endow them with fascinating natural properties such as low cytotoxicity, non-immunogenicity, desirable biocompatibility, speci c targeting capacity and prolonged systemic circulating ability [15,[17][18][19]. These superior properties making them ideal drug delivery nanocarriers.…”