Tumor microenvironment responsive hollow mesoporous Co9S8@MnO2-ICG/DOX intelligent nanoplatform for synergistically enhanced tumor multimodal therapy

Abstract

The development of multifunctional nanoplatform with combination of tumor microenvironment (TME)-responsive dual T₁/T₂ magnetic resonance (MR) imaging and synergistically self-enhanced photothermal/photodynamic/chemo-therapy is of significant importance for tumor theranostic, which still remains a great challenge. Herein, a novel hollow mesoporous double-shell Co₉S₈@MnO₂ nanoplatform loaded with photodynamic agent of indocyanine green molecules (ICG) and chemotherapy drug of doxorubicin (DOX) was designed for TME responsive dual T₁/T₂ enhanced MR imaging and synergistically enhanced anti-tumor therapy. The designed nanoplatform with MnO₂ shell can act as a TME-responsive oxygen self-supplied producer to alleviate tumor hypoxia and simultaneously improve photodynamic therapy (PDT) efficiency. Moreover, the TME-induced MnO₂ dissolving and near-infrared (NIR) triggered photothermal nature from Co₉S₈ shell can further promote the tumor-targeted DOX release, leading to the synergistically improved anti-tumor efficacy. And the simultaneous enhancement in dual T₁/T₂ MR signal was achieved for highly specific tumor diagnosis. The in vivo and in vitro results confirmed that the designed TME-triggered nanoplatform with synergistic combination therapy presented good biocompatibility, and superior inhibition of tumor growth than monotherapy. This study provides the opportunities of designing intelligent TME-activated nanoplatform for highly specific tumor MR imaging and collaborative self-enhanced tumor therapy.

Keywords: Multiple anti-tumor therapy; Oxygen self-supplied producer; Simultaneously enhanced dual T(1)/T(2) MR imaging; TME-Responsive nanoplatform.