MicroRNAs are critical regulators of
cancer initiation, progression, and dissemination. Extensive evidence suggests that the inhibition of over-expressed oncogenic
miRNA function can be a robust strategy for anticancer
therapy. However, in vivo targeted delivery of
miRNA therapeutics to various types of
cancers remains a major challenge. Inspired by their natural synthesis and cargo delivery capabilities, researchers have exploited
tumor cell-derived extracellular vesicles (TEVs) for the
cancer-targeted delivery of
therapeutics and
theranostics. Here, we investigate a TEV-based nanoplatform for multimodal
miRNA delivery and
phototherapy treatments as well as the magnetic resonance imaging of
cancer. We demonstrated loading of anti-miR-21 that blocks the function of endogenous oncogenic miR-21 over-expressed in
cancer cells into and subsequent delivery by TEVs derived from 4T1 cells. We also produced Cy5-anti-miR-21-loaded TEVs from two other
cancer cell lines (HepG2 and SKBR3) and confirmed their robust homologous and heterologous transfection efficiency and intracellular Cy5-anti-miR-21 delivery. Additionally, TEV-mediated anti-miR-21 delivery attenuated
doxorubicin (DOX) resistance in
breast cancer cells with a 3-fold higher cell kill efficiency than in cells treated with DOX alone. We then investigated TEVs as a biomimetic source for the functionalization of
gold-iron oxide nanoparticles (GIONs) and demonstrated nanotheranostic properties of TEV-GIONs in vitro. TEV-GIONs demonstrated excellent T2 contrast in in vitro magnetic resonance (MR) imaging and resulted in efficient photothermal effect in 4T1 cells. We also evaluated the biodistribution and
theranostic property of anti-miR-21 loaded TEV-GIONs in vivo by labeling with
indocyanine green near-infrared
dye. We further validated the
tumor specific accumulation of TEV-GIONs using MR imaging. Our findings demonstrate that the distribution pattern of the TEV-anti-miR-21-GIONs correlated well with the
tumor-targeting capability as well as the activity and efficacy obtained in response to
doxorubicin combination treatments. TEVs and TEV-GIONs are promising nanotheranostics for future applications in
cancer molecular imaging and
therapy.