Monocytic delivery of therapeutic oxygen bubbles for dual-modality treatment of tumor hypoxia

Abstract

Photodynamic therapy (PDT) is a powerful technique photochemically tailored for activating apoptosis of malignant cells. Although PDT has shown promise in several clinical applications, malignant cells in hypoxic regions are often resistant to PDT due to the transport limitation of therapeutics and the oxygen-dependent nature of PDT. Herein, we present an innovative strategy for overcoming the limits of PDT in tumor hypoxia using bone marrow-derived monocytes as cellular vehicles for co-transport of oxygen and red light activatable photosensitizer, chlorin e6 (Ce6). Superparamagnetic iron oxide nanoparticle/Ce6/oxygen-loaded polymer bubbles were prepared and internalized into tumortropic monocytes. These functional bubbles were found harmless to cellular hosts without external triggers. Nevertheless, the therapeutic monocytes exhibited a superior performance in inhibiting tumor growth on Tramp-C1 tumor-bearing mice (C57BL/6J) upon the treatments of tumors with high frequency magnetic field and red light laser (660nm). Histological examinations of the tumor sections confirmed the successful cellular transport of therapeutic payloads to tumor hypoxia and the pronounced antitumor effect elicited by combined hyperthermia/photodynamic therapy along with the additional oxygen supply. This work demonstrates that this oxygen/therapeutic co-delivery via tumortropic monocytes toward tumor hypoxia is promising for improving PDT efficacy.