Ewing's sarcoma microenvironment-sensitive theranostic nanoprobe for image-guided drug delivery

Abstract

Abstract To improve the specificity of the current diagnosis and treatment of Ewing's sarcoma (ES), efforts are underway to develop theranostic targeting probes. In particular, tumor specific markers and microenvironment represent potential targets. In addition, tumor exosomes are considered as possible nanocarriers for drugs to achieve tumor targeting and therapy. Herein, the development of CS2-YK@Exo, by packaging the pH-responsive ES-targeting near-infrared probe CS2-YK into ES exosomes is presented. The engineered exosome can serve as shuttle vehicles for drug uptake by tumor cells, and the pH-activatable characteristics of CS2-YK@Exo in acidic tumor environments can realize a precise image-guided drug delivery for the treatment of ES. The in vivo and in vitro studies verified the targeting, specificity, efficacy, and safety of the probe. Subcutaneous ES tumor mouse models, orthotopic models, and lung metastasis models are established to evaluate the real-time target imaging capabilities of the probe. This study demonstrates the potential of CS2-YK@Exo as a delivery nanosystem for tumor-targeted imaging and release of therapeutics to achieve real-time monitoring of therapy.