Abstract
Extracellular vesicles (EVs), originating from multivesicular bodies by invagination of the endosomal membrane, are communication channels between distant cells. They are natural carriers of exogeneous cellular materials and have been exploited as drug delivery carriers in various diseases. Here, we found that tumor cell-derived EVs can be used as efficient targets in tumors by monitoring with an optical reporter system. Anaplastic thyroid cancer (CAL62) cell-derived EVs with Renilla luciferase (Rluc) were used to target CAL62 tumors in a mouse model. Optical imaging revealed that cancer cell-derived EVs (EV-CAL62/Rluc) targeted the original tumor (CAL62) in mice within 30 min after systemic injection. Furthermore, fluorescence imaging revealed that EV-CAL62/Rluc were internalized into CAL62 tumors in the mice. Ex vivo Optical imaging further confirmed the in vivo finding. Here, we successfully monitored the tumor targeting ability of tumor cell-derived EVs by optical imaging. Based on these results, tumor cell-derived EVs are highly effective natural carriers for drug delivery for cancer therapies.
Highlights
Produced biological nanoparticles are known as extracellular vesicles (EVs)
CAL62 cells transduced with the Renilla luciferase (Rluc) gene were named as CAL62/Rluc and those transduced with the Effluc gene were named as CAL62/Effluc
As the bioluminescent imaging (BLI) signal in CAL62/Rluc and CAL62/Effluc cells increased, there was increase in BLI signal in dose-dependent manner. (Cal62/Rluc: R2 = 0.985; Cal62/Effluc: R2 = 0.976) and no signals were observed in the parental CAL62 cells
Summary
Produced biological nanoparticles are known as extracellular vesicles (EVs). Tumor targeting and selective drug delivery using cancer-derived EVs has been proposed because of their specific expression of tetraspanins, which preferentially interact with certain ligands[18]. Recent studies showed that EVs can be visualized in in vivo animal models by using a lipophilic dye[24], radionuclides[25,26], magnetic particles[27,28] and bioluminescence reporter system[29]. The present study was performed to determine whether EVs can preferentially target their parent cell, which may be useful for tumor targeting and drug delivery. We tested a newly developed bioluminescent EV reporter system in an in vivo animal model to monitor the targeting ability of thyroid cancer-derived EVs to original tumors
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