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Endogenous H2O2 Self-Replenishment and Sustainable Cascades Enhance the Efficacy of Sonodynamic Therapy

Du, Jia-Rui, Teng, Deng-Ke, Wang, Yang, Wang, Qimeihui, Lin, Yuan-Qiang, Luo, Qiang, Xue, Jia-Nan, Zhu, Ling-Yu, Dong, Peng, Zhang, Gen-Mao, Liu, Yan, Sun, Zhi-Xia, Wang, Hui, Sui, Guo-Qing·2023·International Journal of Nanomedicine
DOI 10.2147/ijn.s431221PMC PMC10656771
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Scheme 1 Schematic illustration of PPCH synthesis and tumor therapy.
Scheme 1 Schematic illustration of PPCH synthesis and tumor therapy.CC BY-NC · PubMed Central
Figure 1 (A) Transmission electron microscopy (TEM) and magnification of PPCH. (B) Elemental mapping for PPCH. (C) XRD pattern of PPCH. (D) Size distribution of PP, PPC and PPCH. (E) FTIR spectra of HA, HA-PEG and PPCH.
Figure 1 (A) Transmission electron microscopy (TEM) and magnification of PPCH. (B) Elemental mapping for PPCH. (C) XRD pattern of PPCH. (D) Size distribution of PP, PPC and PPCH. (E) FTIR spectra of HA, HA-PEG and PPCH.CC BY-NC · PubMed Central
Figure 2 (A) Ultraviolet–visible absorption spectra of Ce6, PP and PPCH. (B) Loading efficacy and entrapment efficacy of Ce6. (C) Ce6 controlled release curves of PPCH triggered by different pH values. (D) Schematic presentation of the CAT-like activity of PPCH. (E) Oxygen concentrations in the solutions of different groups. Insert: optical images of oxygen bubbles. (F) Changes in dissolved oxygen concentration after PPCH reacted with different concentrations of H2O2. (G) Ultraviolet–visible absorption spectra of DPBF and PPCH mixed solution with LIFU time. (H) ROS production by PPCH under different conditions. (I) Changes in the hydrated particle size and PDI of PPCH.
Figure 2 (A) Ultraviolet–visible absorption spectra of Ce6, PP and PPCH. (B) Loading efficacy and entrapment efficacy of Ce6. (C) Ce6 controlled release curves of PPCH triggered by different pH values. (D) Schematic presentation of the CAT-like activity of PPCH. (E) Oxygen concentrations in the solutions of different groups. Insert: optical images of oxygen bubbles. (F) Changes in dissolved oxygen concentration after PPCH reacted with different concentrations of H2O2. (G) Ultraviolet–visible absorption spectra of DPBF and PPCH mixed solution with LIFU time. (H) ROS production by PPCH under different conditions. (I) Changes in the hydrated particle size and PDI of PPCH.CC BY-NC · PubMed Central
Figure 3 (A) Confocal microscopy images of M2 macrophages incubated with PPCH. (B) Flow cytometry results of M2 macrophages treated with PPCH. (C) Flow cytometric results of the expression of CD86 (M1 macrophages) and CD206 (M2 macrophages) after treatment with different formulations. (D) Levels of IL-12 released by macrophages before and after regulation of the polarization of M2 macrophages toward M1 macrophages in the different groups. (E) Levels of IL-10 secreted by macrophages in the different treatment groups. (F) Quantitative determination of H2O2 production in the different groups. (G) Intracellular hypoxia imaging using [Ru(dpp)3]Cl2 as an indicator. (H) Flow cytometric and (I) CLSM images of intracellular ROS in 4T1 cells in the different groups.
Figure 3 (A) Confocal microscopy images of M2 macrophages incubated with PPCH. (B) Flow cytometry results of M2 macrophages treated with PPCH. (C) Flow cytometric results of the expression of CD86 (M1 macrophages) and CD206 (M2 macrophages) after treatment with different formulations. (D) Levels of IL-12 released by macrophages before and after regulation of the polarization of M2 macrophages toward M1 macrophages in the different groups. (E) Levels of IL-10 secreted by macrophages in the different treatment groups. (F) Quantitative determination of H2O2 production in the different groups. (G) Intracellular hypoxia imaging using [Ru(dpp)3]Cl2 as an indicator. (H) Flow cytometric and (I) CLSM images of intracellular ROS in 4T1 cells in the different groups.CC BY-NC · PubMed Central
Figure 4 (A) CLSM image and (B) fluorescence intensity image of the subcellular localization of PPCH. (C) CLSM image of 4T1 cells after incubation with PPCH at different pH values (7.4 and 6.5) for 2 h. (D) Relative viability of 4T1 cells incubated with PPCH at different concentrations. (E) Relative viability of 4T1 cells treated with various treatments after LIFU. (F) Calcein-AM and PI stained fluorescence imaging of 4T1 cells subjected to various treatments after LIFU.
Figure 4 (A) CLSM image and (B) fluorescence intensity image of the subcellular localization of PPCH. (C) CLSM image of 4T1 cells after incubation with PPCH at different pH values (7.4 and 6.5) for 2 h. (D) Relative viability of 4T1 cells incubated with PPCH at different concentrations. (E) Relative viability of 4T1 cells treated with various treatments after LIFU. (F) Calcein-AM and PI stained fluorescence imaging of 4T1 cells subjected to various treatments after LIFU.CC BY-NC · PubMed Central
Figure 5 (A) The changes of RBC, WBC, PLT, HGB, ALT, AST, BUN and CR and (B) HE staining sections of mice after injection of PPCH for 5, 15 and 30 d.
Figure 5 (A) The changes of RBC, WBC, PLT, HGB, ALT, AST, BUN and CR and (B) HE staining sections of mice after injection of PPCH for 5, 15 and 30 d.CC BY-NC · PubMed Central
Figure 6 (A) FL images and (B) signal values of PPCH at different time points after i.v. injection of PPCH. (C) FL imaging and (D) quantitative analysis of the intensity of tumor and major organs 24 h after injection of PPCH. In vivo (E) PA images and (F) PA signal intensities of tumors in 4T1 tumor-bearing mice at different time points after i.v. injection of PPCH.
Figure 6 (A) FL images and (B) signal values of PPCH at different time points after i.v. injection of PPCH. (C) FL imaging and (D) quantitative analysis of the intensity of tumor and major organs 24 h after injection of PPCH. In vivo (E) PA images and (F) PA signal intensities of tumors in 4T1 tumor-bearing mice at different time points after i.v. injection of PPCH.CC BY-NC · PubMed Central
Figure 7 (A) CD86 (M1/red), CD206 (M2/green), CD31, HIF-1α, TUNEL and HE staining of tumors after various treatments. (B) Representative flow cytometry plots of M1/M2 macrophages in tumor tissues after various treatments. (C) Oxyhemoglobin level of tumors injected with PPCH before and after different times.
Figure 7 (A) CD86 (M1/red), CD206 (M2/green), CD31, HIF-1α, TUNEL and HE staining of tumors after various treatments. (B) Representative flow cytometry plots of M1/M2 macrophages in tumor tissues after various treatments. (C) Oxyhemoglobin level of tumors injected with PPCH before and after different times.CC BY-NC · PubMed Central
Figure 8 (A) Schematic illustration of the tumor treatment process in vivo. (B) Body weight changes in the different groups. (C) Tumor volume changes in the different groups. (D) Representative photos of tumor tissues dissected from mice after different treatments at day 18. Values of *p < 0.05 and ***p < 0.001.
Figure 8 (A) Schematic illustration of the tumor treatment process in vivo. (B) Body weight changes in the different groups. (C) Tumor volume changes in the different groups. (D) Representative photos of tumor tissues dissected from mice after different treatments at day 18. Values of *p < 0.05 and ***p < 0.001.CC BY-NC · PubMed Central

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Metadata

Authors
Du, J.-R., Teng, D.-K., Wang, Y., Wang, Q., Lin, Y.-Q., Luo, Q., Xue, J.-N., Zhu, L.-Y., Dong, P., Zhang, G.-M., Liu, Y., Sun, Z.-X., Wang, H., & Sui, G.-Q.
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2023-11
Volume
Volume 18
Pages
6667-6687
ISSN
1178-2013
DOI
10.2147/ijn.s431221
PMC
PMC10656771
Cited by
16
References
1
Language
en
Licence
creativecommons.org/licenses/by-nc/3.0/ (unspecified)

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