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

Mol Pharm. 2024 Nov 4;21(11):5864-5879. doi: 10.1021/acs.molpharmaceut.4c00896. Epub 2024 Oct 8.

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.

Keywords: chemodynamic therapy; conformational nanoarchitectures; doping metals; glutathione oxidation; manganese dioxide; molybdenum.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Manganese / chemistry
  • Manganese Compounds* / chemistry
  • Mice
  • Molybdenum* / chemistry
  • Nanoparticles / chemistry
  • Nanostructures / chemistry
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Neoplasms / therapy
  • Oxides* / chemistry
  • Theranostic Nanomedicine* / methods
  • Tissue Distribution
  • Tumor Microenvironment / drug effects

Substances

  • Molybdenum
  • Oxides
  • Manganese Compounds
  • manganese dioxide
  • Manganese
  • Antineoplastic Agents