Fe3O4@SiO2 mesoporous spheres as Fe(ii) donors loaded with artemisinin and a photosensitizer to alleviate tumor hypoxia in PDT for enhanced anticancer therapy

Abstract

Photodynamic therapy (PDT) is an emerging acknowledged alternative treatment for multiple cancers. However, the efficiency of PDT is lower in tumors with imperfect vascular systems under hypoxia because anticancer therapy mediated by reactive oxygen species (ROS) is highly dependent on an adequate and sustained O₂ supply. In this paper, Rattle-type Fe₃O₄@SiO₂ mesoporous spheres are prepared using colloidal carbon spheres as templates to load artemisinin (ART) and the chlorophyll photosensitizer HNPa for localized ROS-generating therapy. HNPa was firstly reported by our group previously as a highly soluble drug and an excellent tissue penetrant. ART was considered to generate ROS based on a pH-mediated Fenton-like process. Our research shows that Fe²⁺ can be easily released from the Fe₃O₄@SiO₂ nanocarrier in the tumor microenvironment by weak acidic etching, and the reaction of ART with Fe²⁺ from Fe₃O₄@SiO₂-ART-HNPa can continue to perform curative functions even in the hypoxic tumor environment after PDT. Moreover, it was found that NIR light irradiation can partly enhance the production of ROS for enhanced anticancer therapy. All these results show the promise of this smart strategy to conquer the existing barriers of PDT.