Multifunctional Nanoplatform for Effective MagneticResonance/Photothermal Dual-Modal Imaging-Guided Synergistic Therapytoward Colon Cancer

Abstract

Colon cancer (CC), featured by its high incidence and mortality rates globally, presents a significant threat to patients worldwide. Traditional treatments often yield unsatisfactory outcomes due to various challenges, such as the hypoxic tumor microenvironment (TME), inadequate tumor targeting, and limited TME responsiveness. To address these issues, a multifunctional nanoplatform, MnO₂-GCDs-Ce6-Cet (MGCC), was fabricated, achieving dual-modal imaging-guided precise treatment of CC. Within MGCC, green fluorescence carbon dots (GCDs) provided excellent photothermal therapy and imaging capacity. The photosensitizer chlorin e6 (Ce6) enhanced MGCC with potent photodynamic therapy (PDT) properties. Additionally, MnO₂ imparted catalase-like activity to MGCC, catalyzing H₂O₂ to produce oxygen, thereby alleviating hypoxia in the TME and enhancing PDT efficacy. MnO₂ also reacted with excess glutathione (GSH) in TME, converting to Mn²⁺, which served as both an MRI contrast agent and a chemodynamic therapy (CDT) agent. To ensure tumor-specific targeting, MnO₂-GCDs-Ce6 was conjugated with cetuximab (Cet), an FDA-approved drug that binds specifically to the epidermal growth factor receptor overexpressed in CC cells. Both in vitro and in vivo experiments demonstrated that MGCC could be specifically delivered to the tumor site, achieving effective MRI and photothermal imaging-guided antitumor effects in CC with excellent biosafety. This study laid the groundwork for the development of a theranostic strategy for CC.