**4. Conclusions**

In summary, Cu-metal organic framework (Cu-MOF)/glucose oxidase (GOD)@hyaluronic acid (HA) (Cu-MOF/GOD@HA) were prepared for chemodynamic therapy (CDT) with the aims to increase H2O2, targeting and efficacy. Cu-MOF/GOD@HA were activated by intracellular GSH and catalyzed intracellular H2O2 reactions to generate ·OH. During these processes, a large amount of ·OH were generated which well facilitates CDT for cancer destruction. The loading of GOD and coating of HA can improve the efficacy of CDT. The present study provides a useful route for the development of nanotherapeutic agents for the treatment of tumor by taking advantage of the intracellular ingredients.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/ 10.3390/nano11071843/s1, Figure S1: (A) SEM image of Cu-MOF. Scar bar: 50 nm. (B) Elemental mapping of C, N, O and Cu of Cu-MOF, Figure S2. (A) FT-IR spectra of Cu-MOF, Cu-MOF/GOD, Cu-MOF/GOD@HA and GOD. (B) TGA curves of Cu-MOF and Cu-MOF/GOD@HA, Figure S3. XRD spectra of Cu-MOF, Cu-MOF/GOD and Cu-MOF/GOD@HA and simulated XRD pattern of Cu-MOF, Figure S4. UV-vis absorption spectra of Cu-MOF and Cu(I)-MOF (The concentrations of pending test samples were 100 μg mL–1). Inset image shows the photographs of the solutions containing Cu-MOF and Cu(I)-MOF, Figure S5. TEM image of Cu-MOF after treatment by GSH, Figure S6. XPS pattern of Cu-MOF (A), Cu-MOF/GOD (B), Cu-MOF/GOD@HA (C), Cu(I)-MOF (D). Cu 2p high-resolution XPS pattern of Cu(I)-MOF (E), Cu-MOF (F), Cu-MOF/GOD (G), Cu-MOF/GOD@HA (H). Figure S7. UV-vis spectra of Cu-MOF+H2O2+MB and MB. Figure S8. (A) GSH depletion after incubation for 1 h in the presence of DTNB (720 μg mL–1) and Cu-MOF (0, 5, 15, 25, 50 μg mL–1). (B) The timedependent reaction of Ampliflu Red solution (600 μg mL–1) with Glu (500 μg mL−1)+Cu-MOF/GOD (100 μg mL–1). (C) The concentration-dependent reaction of Ampliflu Red solution (600 μg mL–1) with Glu+Cu-MOF/GOD (100 μg mL–1) for 30 min (λex/λem = 530/585 nm). Figure S9. (A) The pH values of Cu-MOF+Glu and Cu-MOF/GOD+Glu aqueous solution in different time intervals. Cu-MOF and Cu-MOF/GOD: 100 μg mL–1, Glu: 500 μg mL–1. (B) The pH values of Cu-MOF and Cu-MOF/GOD with different concentration of Glu aqueous solution after 24 h. Cu-MOF/GOD: 100 μg mL–1, Glu: 0, 20, 50, 100, 500, 750, 1000 μg mL–1. Figure S10. ROS staining in MCF-7 cells after incubation with Cu-MOF, Cu-MOF/GOD and Cu-MOF/GOD@HA for 4 h at the concentration of 50 μg mL–1, scale bar: 10 μm. Figure S11. In vivo CDT treatment for MCF-7 cancer cell-bearing mice with different nanocompesites (PBS, Cu-MOF, Cu-MOF/GOD and Cu-MOF/GOD@HA 2.5 mg kg–1). (A) The changes of body weight for the KunMing mice during the process of therapy. (B) The variation of tumor size for the KunMing mice during the process of therapy. (C) The average relative mass excised from MCF-7 tumor-bearing mice after the treatment. (D) Photographs showing the tumor size after the treatment. Scale bar, 1 cm. (E) H&E staining of the major organs/tissues of mice after CDT process. Scale bar, 50 μm. Values of *p* < 0.05 were considered statistically significant, with ∗, ∗∗, ∗∗∗ represent *p* < 0.05, *p* < 0.01, and *p* < 0.001, respectively. 1, 2, 3 and 4 represent the group of PBS, Cu-MOF,Cu-MOF/GODandCu-MOF/GOD@HA,respectively.FigureS12.Hemolysispercentage

of RBCs by Cu-MOF/GOD@HA nanodots at various concentration levels (10–100 μg mL–1). Inset: the photographs for direct observation of hemolysis.

**Author Contributions:** Y.-N.H.: Conceptualization, Writing-Original Draft, Writing-Review & Editing. C.-C.Q.: Formal analysis, Investigation, Writing-Review & Editing. Y.S.: Conceptualization, Resources, Project administration, Writing-Review & Editing, Funding acquisition. J.-H.W.: Conceptualization, Resources, Writing-Review & Editing, Supervision, Funding acquisition. W.C.: Conceptualization, Resources, Writing-Review & Editing, Supervision. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Data Availability Statement:** The details regarding where data supporting reported results can be obtained from the authors.

**Acknowledgments:** This work is financially supported by the Natural Science Foundation of China (21974018, 21727811 and 22074011), Fundamental Research Funds for the Central Universities (N2005015, and N2005027), and Liaoning Revitalization Talents Program (XLYC1907191, XLYC1802016).

**Conflicts of Interest:** The authors declare no conflict of interest.
