Exosomes separated based on the “STOP” criteria for tumor-targeted drug delivery

Abstract

Exosomes, a class of natural nanoparticles, have recently been used for drug delivery. To move from bench to bedside, exosomes should meet the “STOP” criteria: (1) high Safety; (2) good Targeting ability; (3) rapid Obtainment; and (4) high Purity. To the best of our knowledge, however, no studies on exosomes that can satisfy all the abovementioned criteria have been reported to date. In this study, an optimized superparamagnetic nanoparticle cluster (SMNC)-based method was used to easily achieve the abovementioned objective. Multiple superparamagnetic nanoparticles (SPMNs) labeled by holo-transferrin with PEG spacers anchor onto an exosome to form an upgraded exosome-based superparamagnetic nanoparticle cluster (denoted SMNC-EXO-PLUS). SMNC-EXO-PLUSs separated exosomes from healthy animal blood to ensure high safety, and their formation based on the specific binding of SPMNs to exosomes endowed exosomes with high purity. In addition, SMNC-EXO-PLUSs possessed strong magnetic response, realizing their rapid obtainment and good targeting ability. The results demonstrated that the cell viability was maintained as high as 88% in a 1000 μg mL⁻¹ SMNC-EXO-PLUS solution, and the time interval from the extraction of blood to the acquisition of purified exosomes could be reduced to 3.5 h. Furthermore, the effects of in vivo tumor inhibition of drug-loaded SMNC-EXO-PLUSs (denoted as D-SMNC-EXO-PLUSs) were pronounced. Based on the “STOP” criteria, we exploited a new exosome-related drug delivery vehicle, dramatically promoting the clinical translation of exosomes.