MnO₂-Disguised Upconversion Hybrid Nanocomposite: An Ideal Architecture for Tumor Microenvironment-Triggered UCL/MR Bioimaging and Enhanced Chemodynamic Therapy

Abstract

Upconversion nanoparticles (UCNPs) and MnO 2 hybrid theranostic nanoplatform (UCMn) is highly desired; however, the rational design of such UCMn hybrid nanomaterials is still a great challenge. Herein, a simple and versatile strategy for the in situ growth of MnO 2 on the surfaces of UCNPs was reported using a sacrificial template method to construct an ideal MnO 2 -disguised and tumor microenvironment−triggered architecture. Such sophisticated architecture not only achieves activatable magnetic resonance imaging and restorable upconversion luminescence (UCL) imaging with over 100-fold enhancement of UCL in vivo but also significantly improves the efficiency of chemodynamic therapy (CDT) by glutathione depletion-and cisplatinactivation-enhanced • OH generation simultaneously. Additionally, the synergetic effect of CDT and chemotherapy presents excellent therapeutic effect in vivo as compared to either CDT or chemotherapy alone. We believe that the ideal design of the MnO 2 -disguised upconversion hybrid nanocomposite will provide more revelations on the future research on nanoscale theranostic systems.

Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications

“…Moreover, compared with Mn 2+ ‐mediated CDT, MnO 2 is able to generate more •OH and show higher cytotoxicity demonstrated with both in vitro and in vivo studies because of GSH depletion by MnO 2 . After that, more researches further proved the ability of MnO 2 for CDT 21,46d. Furthermore, Cai group also confirmed that MnO NPs have the capacity of producing free radical for CDT …”

“…Furthermore, it is worth noting that different valences of manganese ions exhibit discrepant toxicity. For example, compared with Mn 2+ ions, it has been proved that MnO 2 (Mn 4+ ions) at the same manganese content showed higher cancer cells killing due to GSH depletion by MnO 2 6c,21. In short, for biomedical applications, manganese valence states among oxides are very important.…”

“…As presented in Table , MONs and MON‐based composite materials all exhibit high cell viability under a certain concentration, suggesting that they possess low cytotoxicity and good biocompatibility. However, despite that, it is worth noting that some reports have testified that MONs could serve as CDT agents and intrinsically exhibited cytotoxicity to tumor cells at a certain doses via a H 2 O 2 /GSH‐dependent Fenton‐like reaction 6c,21,89. Luckily, this effect on normal cells is negligible because of low levels of H 2 O 2 /GSH contents compared with tumor cells and thus MONs still possess low cytotoxicity on normal cells.…”

“…It is well known that hypoxia and GSH overproduction within solid tumors tremendously limit PDT efficacy due to the O 2 ‐dependent therapeutic pattern and potent scavenging effect of GSH on ROS . Fortunately, MON‐based nanomaterials can effectively overcome the two obstacles for enhanced PDT efficiency by producing O 2 or/and depleting GSH.…”

Nanomaterials for the regulation of the tumor microenvironment and theranostics

“…Aiming at solving this restriction, several nanomaterials with GSHconsumption ability have been developed and used for tumor theranostics. [78][79][80][81] Li et al prepared copper-amino acid mercaptide NPs (Cu-Cys NPs) with GSH-triggered and H 2 O 2 -enhanced CDT abilities for resisting breast tumors ( Fig. 11A and B).…”