Constructing Electron Levers in Perovskite Nanocrystals to Regulate the Local Electron Density for Intensive Chemodynamic Therapy

Abstract

The local electron density of an atom is one key factor that determines its chemical properties.R egulating electron density can promote the atomsr eactivity and so reduce the reaction activation energy,whichishighly desired in many chemical applications.H erein, we report an intracrystalline electron lever strategy,w hich can regulate the electron density of reaction centre atoms via manipulating ambient lattice states,f or Fenton activity improvement. Typically,with the assistance of ultrasound, the Mn 4+ ÀOÀFe 3+ bond in BiFe 0.97 Mn 0.03 O 3 perovskite nanocrystals can drive valence electrons and free electrons to accumulate on Fe atoms by apolarization electric field originated from the designed lattice strain. The increase of electron density significantly improves the catalytic activity of Fe,d ecreasing the activation energy of BiFe 0.97 Mn 0.03 O 3-mediated Fenton reaction by 52.55 %, and increasing the COH yield by 9.21-fold. This study provides an ew wayt ou nderstand the sono-Fenton chemistry,a nd the increased COH production enables ah ighly effective chemodynamic therapy.

Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic‐Synergized Multimodal Therapy

“…[ 23 ] CDT provides unique superiorities compared with other cancer treatments, but the relatively limited treatment benefits largely compromise its wide clinical application in cancer treatment. Generally, CDT efficacy depends on the reaction rate of the introduced Fenton/Fenton‐like reaction, which is usually influenced by the metal catalyst, [ 24 ] H 2 O 2 concentration, [ 25 ] pH, [ 26 ] and external energy field. [ 27 ] Accordingly, various strategies by manipulating the limiting factors to reinforce the intratumoral Fenton/Fenton‐like reaction have been designed and reported to enhance CDT performance for maximizing the tumor therapeutic efficacy.…”

“…This IEL strategy can locally manipulate electron density of reaction center atoms via regulating ambient lattice states, thereby reducing the activation energy of Fe 3+ for ECDT. [ 25 ] In this design, a Mn 4+ ‐doped bismuth ferrite (Bi–Fe 0.97 Mn 0.03 O 3 , MBFO) nanocrystal was developed. The formative Mn 4+ OFe 3+ bond in the MBFO can stimulate valence electrons and free electrons to enrich on Fe atoms for increased local electron density, thus resulting in improved catalytic activity of Fe, decreased Fe 3+ activation energy, and increased •OH generation.…”

Nanocatalyst‐Mediated Chemodynamic Tumor Therapy

“…[59] Compared with Fe 3 O 4 PCs, Fe 3 O 4 MCs exhibited higher peroxidase-like activity to yield plenty of •OH because of the larger specific surface area, which results in a higher ratio of Fe 2+ /Fe 3+ and more oxygen defects. At the same time, the mesocrystalline structure of Fe 3 O 4 MCs provided higher magnetocaloric conversion efficiency than that Fe-based nanocatalysts Fe 3 O 4 @Bi 2 S 3 Photothermal-enhanced CDT [56] BSO-FeS 2 NPs Photothermal-assisted, inhibiting the synthesis of GSH [57] CuS−Fe@polymer Boost transformation of Fe 3+ into Fe 2+ [58] Fe 3 O 4 mesocrystals Enhanced PDO-like activity, magnetic hyperthermia-assisted CDT [59] AFeNPs Raising the ionization rate of catalysts [60] Au/FeMOF@CPT NPs Improving H 2 O 2 level in TME [63] GOx@ZIF@MPN Accelerating Fe 3+ /Fe 2+ conversion [51] FPS-PVP NSs PTT-enhanced CDT by NIR-II light irradiation [67] UCNP@Silica@ZnFe 2 O 4 NIR-accelerated Fe 3+ /Fe 2+ conversion [ 132] TPZ/Fe 3 O 4 @MSN-GOx GOx-enhanced CDT, combined with chemotherapy [91] AFeNPs@CAI Reducing the acidity of the TME [92] Ec-pE@MNP Generating H 2 O 2 via bacterial metabolism [ 101] DOX@Fe(III)@WS 2 -PVP Accelerating Fe 3+ /Fe 2+ conversion; combined with PTT and chemotherapy [ 124] BiFe 0.97 Mn 0.03 O 3 Accumulating electrons of Fe atom to improve the catalytic efficiency [ 134] Cu-based nanocatalysts CP NCs Occur Fenton reaction in the pH value of TME, PTT-enhanced CDT [70] BSA-CuFeS 2 Efficient •OH generation in a weak acidic condition [72] CS-GOD@CM nanocatalysts Improving H 2 O 2 level; NIR-assisted Fenton reaction [68] PEGylated Cu 2−x S nanodots Efficient •OH generation in weak acidic environment [71] copper peroxide nanoparticles (CP) Directly introducing H 2 O 2 in vivo [97] Mn-based nanocatalysts MS@MnO 2 NPs Consuming GSH for enhanced CDT [ 110] H-MnCO 3 /Ce6-PEG Synergistic PDT and CDT [75] Janus Au-MnO nanoparticles Synergistic CDT and SDT [76] Co-based nanocatalysts PZIF67-AT(Co) Improving H 2 O 2 level via disrupting the H 2 O 2 metabolism [ 102] Ag-based nanocatalysts PCN@AgNPs@NM NIR light-triggered Ag + release for improving the ROS level [ 122] of Fe 3 O 4 PCs under the action of the magnetic field. The absorption rate could reach 722 w g -1 at an Fe concentration of 0.6 mg mL -1 .…”

“…Inspired by this, Bu et al proposed a novel intracrystalline electron lever (IEL) strategy for improving the efficiency of CDT (Figure 12A). [134] They constructed the electron lever by synthesizing 3% Mn 4+ -doped bismuth ferrite nanocrystals (BiFe 0.97 Mn 0.03 O 3 , MBFO). The Mn 4+ -O-Fe 3+ bond in MBFO perovskite nanocrystals could transfer free electrons and valence electrons to accumulate on Fe atoms with the assistance of ultrasound, which further improved the catalytic activity of Fe for increasing the •OH production.…”

An amino acid-based supramolecular nanozyme by coordination self-assembly for cascade catalysis and enhanced chemodynamic therapy towards biomedical applications

“…Chemodynamic therapy (CDT), which can convert less reactive hydrogen peroxide (H 2 O 2 ) into most harmful hydroxyl radical (•OH) through the metal catalysts (e.g., Fe 2+ , Mn 2+ , Cu + ) -mediated Fenton reaction or Fenton-like reaction [1][2][3][4][5] , is considered to be a promising novel modality for relevant diseases (e.g., cancer, pathogenic bacterial infection) because of its local selectivity and negligible side effect [6][7] . However, the therapeutic outcomes of CDT have been highly limited due to the insufficiencies of endogenous H 2 O 2 [8][9][10] , which significantly comprises the antitumor or antimicrobial effects. Therefore, the incorporation of a H 2 O 2 -supplementing functionality into conventional CDT strategies have been exploited for potentiating their therapeutic efficiencies [11][12] .…”