Manipulation of endogenous exosome biodistribution for the treatment of diseases

The systemic biodistribution of endogenous extracellular vesicles is central to the maintenance of tissue homeostasis. Here, researchers from Xi’an Jiao Tong University show that angiogenesis and heart function in infarcted heart tissue can be ameliorated by the local accumulation of exosomes collected from circulation using magnetic nanoparticles. The nanoparticles consist of a Fe₃O₄ core and a silica shell that is decorated with poly (ethylene glycol) conjugated through hydrazone bonds to two types of antibody, which bind either to CD63 antigens on the surface of extracellular vesicles or to myosin-light-chain surface markers on injured cardiomyocytes. On application of a local magnetic field, accumulation of the nanoparticles and cleavage of the hydrazone bonds under the acidic pH of injured cardiac tissue lead to the local release of the captured exosomes. In rabbit and rat models of myocardial infarction, the magnetic-guided accumulation of captured CD63-expressing exosomes in infarcted tissue led to reductions in infarct size as well as improved left-ventricle ejection fraction and angiogenesis. The approach could be used to manipulate endogenous exosome biodistribution for the treatment of other diseases.

Schematic of the vesicle-shuttle approach

The anti-CD63 antibodies conjugated to the vesicle shuttle capture and attach to endogenous circulating exosomes (i). Dual targeting of the GMNP_EC using both an external magnet, which attracts the magnetic vesicle shuttle to the infarct area, and a conjugated anti-MLC antibody, which targets MLC on damaged cardiomyocytes (ii). Release of the exosomes triggered by the infarct environment of pH < 6.8, acidosis-induced cleavage of hydrazone bonds and shedding of the GMNP_EC corona leads to the selective release of exosomes (iii).