Synergistic ROS Generation via Core–Shell Nanostructures with Increased Lattice Microstrain Combined with Single-Atom Catalysis for Enhanced Tumor Suppression

This study emphasizes the innovative application of FePt and Cu core–shell nanostructures with increased lattice microstrain, coupled with Au single-atom catalysis, in significantly enhancing •OH generation for catalytic tumor therapy. The combination of core–shell with increased lattice microstrain and single-atom structures introduces an unexpected boost in hydroxyl radical (•OH) production, representing a pivotal advancement in strategies for enhancing reactive oxygen species. The creation of a core–shell structure, FePt@Cu, showcases a synergistic effect in •OH generation that surpasses the combined effects of FePt and Cu individually. Incorporating atomic Au with FePt@Cu/Au further enhances •OH production. Both FePt@Cu and FePt@Cu/Au structures boost the O2 → H2O2 → •OH reaction pathway and catalyze Fenton-like reactions. This enhancement is underpinned by DFT theoretical calculations revealing a reduced O2 adsorption energy and energy barrier, facilitated by lattice mismatch and the unique catalytic activity of single-atom Au. Notably, the FePt@Cu/Au structure demonstrates remarkable efficacy in tumor suppression and exhibits biodegradable properties, allowing for rapid excretion from the body. This dual attribute underscores its potential as a highly effective and safe cancer therapeutic agent.

a The S0 2 factor (0.9818) of sample FePt@Cu/Au was applied using a reference Cu foil.ΔE 0 was refined as a global fit parameter, returning a value of 6.5 ± 1.6 eV.The data range covered 3 ≤ k ≤ 13 Å -1 and 1.6 ≤ R ≤ 3.2 Å.There were 7 variable parameter out of a total of 9.9 independent points.The R factor for this fit was 0.6%.b The distances for Cu-Cu1 and Cu-Au1 were from the FeFF file of CuAu.c The coordination numbers were constrained as follow: N(Cu-Cu1)=12, N(Cu-Cu2)=6, N(Cu-Cu3)=24 and N(Cu-Cu1-Cu1)=48 to determine the relative S0 2 applied to the sample FePt@Cu/Au.a The S0 2 factor (0.7465) of sample FePt@Cu/Au was applied using a reference Au foil.ΔE 0 was refined as a global fit parameter, returning a value of 2.3 ± 1.2 eV.The data range covered 3 ≤ k ≤ 10 Å -1 and 1.0 ≤ R ≤ 3.5 Å.There were 7 variable parameter out of a total of 11.0 independent points.The R factor for this fit was 0.52%.b The distances for Au-Cu1 and Au-Au1 were from the FeFF file of CuAu.c The coordination numbers were constrained as follow: N(Au-Au1)=12, N(Au-Au2)=6, N(Au-Au3)=24 and N(Au-Au1-Au1)=48 to determine the relative S0 2 applied to the sample FePt@Cu/Au.        Figure S11 The morphology of FePt@Cu/Au@SA nanocubes treated with HepG2 cancer cells for 24 hours.
Figure S12 a, Analysis of hemolysis in blood containing 2% red blood cells from FePt@Cu/Au@SA nanocubes.Negative and positive controls conducted by immersing red blood cells in PBS and water, respectively.b, Cytotoxicity analysis of vascular endothelial cells treated with FePt@Cu/Au@SA nanocubes.All data were obtained in triplicate.

Figure S13
Examining the biosafety of FePt@Cu/Au@SA treatments in C57BL/6 mice.a, Daily monitoring of body weight changes in the PBS-treated group and mice treated with FePt@Cu/Au@SA was conducted for up to 7 days (n=3).b, On the 7th day post-injection, blood biochemical analysis was performed on mice (n=3).c, Histological morphology of each organ was observed on the 7th day post-injection using H&E staining (Scale bar, 200 µm) (n=3).

Figure
Figure S1 a, HR-TEM image of the FePt nanoparticles and b, the corresponding EDS signals of Fe and Pt from white cross as indicated in above (a).The other signals belong to the TEM nickel grid support composed of a carbon and silicon film.

Figure
Figure S2 a, HR-TEM image of the single FePt@Cu/Au nanocube and the corresponding EDS mapping of Cu (red), Pt (pink), Au (yellow) and Fe (green).b, The corresponding EDS signals of Cu, Fe, Pt and Au from red cross.

Figure S3 .Figure S4 .
Figure S3.The characteristics of Au nanocubes.a, TEM image; b, Size distribution in edge length of Au nanocubes.

Figure S5 .
Figure S5.The magnified image of Figure 2a showing high resolution of AC HAADF-STEM image of the FePt@Cu/Au nanocube.

Figure
Figure S6 k 2 -weighted EXAFS spectra of a, Cu K-and b, Au L 3 -edge; Fourier Transforms at c, Cu K-and d, Au L 3 -edge of FePt@Cu/Au nanocubes.

Figure S8
Figure S8The efficiency of •OH generation at different pH levels (5 and 7) was detected by measuring TPA fluorescence intensity under varying concentrations.

Figure
Figure S14 Body weight changes of HepG2-Red-FLuc orthotopic tumor mice in each treatment group (n=4).

Table S1 :
Curve-fit Parameter a for Cu K-edge EXAFS for FePt@Cu/Au.

Table S2 :
Curve-fit Parameter a for Au L 3 -edge EXAFS for FePt@Cu/Au.