Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

Abstract

Treating the hypoxic region of the tumor remains a significant challenge. The goals of this study are to develop an exosome platform that can target regions of tumor hypoxia and that can be monitored in vivo using magnetic particle imaging (MPI). Four types of exosomes (generated under hypoxic or normoxic conditions, and with or without exposure to X-ray radiation) were isolated from MDA-MB-231 human breast cancer cells. Exosomes were labeled by DiO, a fluorescent lipophilic tracer, to quantify their uptake by hypoxic cancer cells. Subsequently, the exosomes were modified to carry SPIO (superparamagnetic iron oxide) nanoparticles and Olaparib (PARP inhibitor). FACS and fluorescence microscopy showed that hypoxic cells preferentially take up exosomes released by hypoxic cells, compared with other exosome formulations. In addition, the distribution of SPIO-labeled exosomes was successively imaged in vivo using MPI. Finally, the therapeutic efficacy of Olaparib-loaded exosomes was demonstrated by increased apoptosis and slower tumor growth in vivo. Our novel theranostic platform could be used as an effective strategy to monitor exosomes in vivo and deliver therapeutics to hypoxic tumors.

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

“…An interesting example of active loading of probes is the use of transporter proteins on the membrane of exosomes. A study reported the encapsulation of glucose-coated gold nanoparticles by the GLUT1 glucose transporter on the exosomal membrane [75]. Additional transporters are expected to be available for the specific encapsulation of probes in exosomes obtained from different sources with the advancement of research.…”

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

“…Different cells under different conditions determine the heterogeneity of EVs, and different cell-derived EVs may be home to specific tissues (Thery et al, 1999;Colombo et al, 2014). For instance, EVs derived from hypoxic tumor cells tend to be taken up by hypoxic tumor cells (Jung et al, 2018). Again, central nervous system-derived EVs can cross the BBB and serve as a unique DDS for specific neuron populations .…”

“…As 'molecule carrier', EVs may serve as novel tools for various therapeutic and diagnostic purpose (EL Andaloussi et al, 2013;Ohno et al, 2016), such as anti-tumor therapy (Poggio et al, 2019), immune-modulatory (Buzas et al, 2014), and drug delivery (Gudbergsson et al, 2019). As a drug delivery vesicle, EVs have been tested for the delivery of siRNAs (El-Andaloussi et al, 2012), miRNAs (Li et al, 2019c), proteins (Haney et al, 2015), small molecule drugs (Zhuang et al, 2011), nanoparticles (Jung et al, 2018), and CRISPR/Cas9 into animal models. Owing to their natural origin, EVs are born with high biocompatibility, enhanced stability, and limited immunogenicity, which provide potential advantages over traditional synthetic delivery vehicles, such as liposomes and nanoparticles.…”

MRI tracking reveals selective accumulation of stem cell-derived magneto-extracellular vesicles in sites of injury

“…Before this, EV imaging and tracking methods can serve as a guide to direct the development, optimization, and implementation of EV-based therapeutics. To date, considerable effort has been devoted to develop EV tracking methods using fluorescence imaging (14,15), bioluminescence imaging (16), single-photon emission computed tomography (SPECT) (17), positron emission tomography (PET) (18), computed tomography (CT) (19,20), magnetic resonance imaging (MRI) (21,22), and magnetic particle imaging (23). Among them, MRI is an appealing imaging modality that is used widely in the clinic and has excellent soft-tissue contrast without using ionizing radiation.…”