Development of multifunctional MnO2-based nanoplatforms for hypoxia modulation/T1-weighted MRI/ optical biosensing and targeted drug delivery

Abstract

TME-responsive MnO2 nanorod-based platform was synthesized through the simple and eco-friendly hydrothermal approach. Then, chitosan cross-linked tripolyphosphate (Chi-TPP) was applied to coat the surface of the MnO2 nanorod to enhance the biocompatibility of bare nanostructures. The high specific surface area (51.966 m2/g) and heterogeneous nature of MnO2@Chi-TPP nanoplatforms demonstrated a significant physical loading capacity of pharmaceutical cargo (97.116 mg/g). In-vitro release profiles demonstrated that the release of DOX and the Fenton-like reaction for enhanced therapeutic effect were induced by the demolition of MnO2 nanorod to Mn2+ under acidic conditions and high glutathione (GSH), high temperature, and high concentration of H2O2. Additionally, Mn2+ ions could function as a T1-weighted MRI contrast agent. As-synthesized nanoplatforms not only serve as a TME-responsive nanocarrier but also introduces a TME-modulating agent to produce molecular O2 and simultaneously decrease tumor hypoxia. To precise detection of the tumor microenvironment, fluorescein isothiocyanate (FITC) was well labeled on the MnO2@Chi-TPP nanoplatform. The MnO2 nanorods are known as a fluorescence signal quencher regardless of the wide absorption band in the visible spectrum through the fluorescence resonance energy transfer (FRET) effect. The in-vitro analysis proved the TME-responsiveness of the MnO2@Chi-TPP@FITC nanosystem. The recovery of the fluorescence signal in the TME introduced the MnO2@Chi-TPP@FITC nanosystem as a “turn off-on” sensor.