A multifunctional nanotheranostic for the intelligent MRI diagnosis and synergistic treatment of hypoxic tumor.

Abstract

Hypoxia, as an inevitable characteristic of solid tumors, has been regarded as a noticeably causative factor to therapeutic resistance and metastatic variants. Exploring novel theranostics to realize the accurate diagnosis of hypoxia and the simultaneous implementation of effective therapy is a promising prospect for the successful treatment of tumors. In the present study, we designed and synthesized a multifunctional rattle-structured nanotheranostic, with the inner core coated by hollow mesoporous silica for chemical drug Doxorubicin (DOX) storage and hypoxia-sensitive MnO₂ enrichment. In various acidic micro-environments caused by hypoxia, MnO₂ nanosheets could be degraded into manganese ions (Mn²⁺), which were chelated by the modified Tetraxetanum (DOTA) ligands for real-time T₁-magnetic resonance imaging (T₁-MRI), with on-demand DOX release to realize both normoxia and hypoxia-sensitive chemotherapy by overcoming hypoxia. Nanotheranostics integrating hypoxia-driven T₁-MRI with synergetic chemotherapy have tremendous potential in the intelligent diagnosis, personalized treatment and excellent prognosis of solid tumors in the future.