Transition Metal (Molybdenum)-Doped Drug-like Conformational Nanoarchitectonics with Altered Valence States (Mn2+/Mn4+ and Mo5+/Mo6+) for Augmented Cancer Theranostics.

Abstract

Despite the advancements in cancer therapy, delivering active pharmaceutical ingredients (APIs) using nanoparticles remains challenging due to the failed conveyance of the required drug payload, poor targeting ability, and poor biodistribution, hampering their clinical translation. Recently, the appropriate design of materials with intrinsic therapeutic functionalities has garnered enormous interest in the development of various intelligent therapeutic nanoplatforms. In this study, we demonstrate the fabrication of transition metal (molybdenum, Mo)-doped manganese dioxide (MnO₂) nanoarchitectures, exhibiting diagnostic (magnetic resonance imaging, MRI) and therapeutic (chemodynamic therapy, CDT) functionalities. The facile hydrothermal approach-assisted Mo-doped MnO₂ flower-like nanostructures offered tailorable morphologies in altered dimensions, precise therapeutic effects, exceptional biocompatibility, and biodegradability in the tumor microenvironment. The resultant defects due to doped Mo species exhibited peroxidase and oxidase activities, improving glutathione (GSH) oxidation. The two sets of variable valence metal ion pairs (Mn²⁺/Mn⁴⁺ and Mo⁵⁺/Mo⁶⁺) and their interplay could substantially improve the Fenton-like reaction and generate toxic hydroxyl radicals (^•OH), thus achieving CDT-assisted antitumor effects. As inherent T1-MRI agents, these MnO₂ nanoparticles displayed excellent MRI efficacy in vitro. Together, we believe that these conformational Mo-doped MnO₂ nanoarchitectures with two pairs of variable valence states could potentiate drugless therapy in pharmaceutics.