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Hypoxia and Singlet Oxygen Dual-Responsive Micelles for Photodynamic and Chemotherapy Therapy Featured with Enhanced Cellular Uptake and Triggered Cargo Delivery

Guo, Xuliang, Han, Lefei, Chen, Wenyu, He, Huixin, Zhang, Weijin, Huang, Chaoqi, Wang, Xiu·2024·International Journal of Nanomedicine
DOI 10.2147/ijn.s432407PMC PMC10790668
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Scheme 1 Hypoxia- and singlet oxygen-responsive polymeric micelles for in tegration of photodynamic and chemotherapy therapy in a tumor-bearing mice model.
Scheme 1 Hypoxia- and singlet oxygen-responsive polymeric micelles for in tegration of photodynamic and chemotherapy therapy in a tumor-bearing mice model.CC BY-NC · PubMed Central
Figure 1 Physicochemical properties of hypoxia and singlet oxygen-responsive micelles (n = 3). (A) The hydrodynamic size of DHM-Ce6 and DHM-Ce6@TPZ. Transmission electron microscope images of DHM-Ce6 (B) and DHM-Ce6@TPZ (C) (scale bar: 500 nm). (D) UV-vis absorption spectra of Ce6, TPZ, DHM, DHM-Ce6, and DHM-Ce6@TPZ. (E) Normalized absorbance of DPBF at 411 nm of different formulations with light irradiation. (F) TEM image of DHM-Ce6@TPZ micelles post laser treatment (660 nm, 200 mW/cm2, 10 min). Scale: 500 nm. (G) The UV-vis spectra of DHM-Ce6@TPZ treated with sodium dithionite (10 mM). TPZ release from DHM-Ce6@TPZ micelles under mimicked hypoxia conditions. (H) (10 mM sodium dithionite), and under laser irradiation conditions (I) (660 nm, 200 mW/cm2, 10 min).
Figure 1 Physicochemical properties of hypoxia and singlet oxygen-responsive micelles (n = 3). (A) The hydrodynamic size of DHM-Ce6 and DHM-Ce6@TPZ. Transmission electron microscope images of DHM-Ce6 (B) and DHM-Ce6@TPZ (C) (scale bar: 500 nm). (D) UV-vis absorption spectra of Ce6, TPZ, DHM, DHM-Ce6, and DHM-Ce6@TPZ. (E) Normalized absorbance of DPBF at 411 nm of different formulations with light irradiation. (F) TEM image of DHM-Ce6@TPZ micelles post laser treatment (660 nm, 200 mW/cm2, 10 min). Scale: 500 nm. (G) The UV-vis spectra of DHM-Ce6@TPZ treated with sodium dithionite (10 mM). TPZ release from DHM-Ce6@TPZ micelles under mimicked hypoxia conditions. (H) (10 mM sodium dithionite), and under laser irradiation conditions (I) (660 nm, 200 mW/cm2, 10 min).CC BY-NC · PubMed Central
Figure 2 Confocal images of cellular uptake by 4T1 cells under normoxia or hypoxia at 2, 4, and 6 h post DHM-Ce6@TPZ micelles incubation (scale bar: 20 μm, n = 3).
Figure 2 Confocal images of cellular uptake by 4T1 cells under normoxia or hypoxia at 2, 4, and 6 h post DHM-Ce6@TPZ micelles incubation (scale bar: 20 μm, n = 3).CC BY-NC · PubMed Central
Figure 3 Viability of 4T1 cells in response to different formulations treatment under normoxia or hypoxia.(n = 4) (A) DHM-Ce6@TPZ without laser irradiation under normoxia or hypoxia. (B) DHM-Ce6 with laser irradiation under normoxia or hypoxia. (C) DHM-Ce6@TPZ without laser irradiation under normoxia or hypoxia. (D) Imaging of living and dead cells upon formulation treatment with the fixed TPZ dose at 1 μg/mL. The cells were stained with Calcein AM (green, live cells) and PI (red, dead cells) (scale bar: 20 μm).
Figure 3 Viability of 4T1 cells in response to different formulations treatment under normoxia or hypoxia.(n = 4) (A) DHM-Ce6@TPZ without laser irradiation under normoxia or hypoxia. (B) DHM-Ce6 with laser irradiation under normoxia or hypoxia. (C) DHM-Ce6@TPZ without laser irradiation under normoxia or hypoxia. (D) Imaging of living and dead cells upon formulation treatment with the fixed TPZ dose at 1 μg/mL. The cells were stained with Calcein AM (green, live cells) and PI (red, dead cells) (scale bar: 20 μm).CC BY-NC · PubMed Central
Figure 4 Fluorescence imaging of total reactive oxygen species (ROS) in 4T1 cells upon formulation treatment under different conditions, ROS was performed using a DCFH-DA probe (scale bar: 50 μm) with the dose of TPZ fixed at 1 μg/mL (n = 3).
Figure 4 Fluorescence imaging of total reactive oxygen species (ROS) in 4T1 cells upon formulation treatment under different conditions, ROS was performed using a DCFH-DA probe (scale bar: 50 μm) with the dose of TPZ fixed at 1 μg/mL (n = 3).CC BY-NC · PubMed Central
Figure 5 Kinetic biodistribution of micellar formulations in 4T1 tumor-bearing mice (n = 3). (A) In vivo kinetic fluorescence of Cy5 in 4T1 tumor-bearing mice up to 24 h after intravenous injection of free Cy5, DHM@Cy5 micelles. (B) Kinetic fluorescence quantification regarding Cy5 in tumors. (C) Semi-quantitative fluorescence summary of Cy5 level in healthy organs and tumors at the end of the biodistribution study. ***p < 0.001. (D) Ex vivo fluorescent analysis of Cy5 in tumors and other healthy organs 24 h post-dose administration.
Figure 5 Kinetic biodistribution of micellar formulations in 4T1 tumor-bearing mice (n = 3). (A) In vivo kinetic fluorescence of Cy5 in 4T1 tumor-bearing mice up to 24 h after intravenous injection of free Cy5, DHM@Cy5 micelles. (B) Kinetic fluorescence quantification regarding Cy5 in tumors. (C) Semi-quantitative fluorescence summary of Cy5 level in healthy organs and tumors at the end of the biodistribution study. ***p < 0.001. (D) Ex vivo fluorescent analysis of Cy5 in tumors and other healthy organs 24 h post-dose administration.CC BY-NC · PubMed Central
Figure 6 In vivo antitumor efficacy of dual-responsive micelles (n = 5). (A) Tumor-growth inhibitory effects of seven formulations. (B) Quantitative analysis of tumor weight. (C) Images of tumors in the end of treatment. (D) Changes in body weight of mice during treatments. (E) TUNEL staining (scale bar: 50 μm) and H&E staining (scale bar: 100 μm) at the end of therapy. **p < 0.01; ***p < 0.001.
Figure 6 In vivo antitumor efficacy of dual-responsive micelles (n = 5). (A) Tumor-growth inhibitory effects of seven formulations. (B) Quantitative analysis of tumor weight. (C) Images of tumors in the end of treatment. (D) Changes in body weight of mice during treatments. (E) TUNEL staining (scale bar: 50 μm) and H&E staining (scale bar: 100 μm) at the end of therapy. **p < 0.01; ***p < 0.001.CC BY-NC · PubMed Central
Figure 7 Histological analysis of major healthy organs (heart, liver, spleen, lung, and kidney) at the end of efficacy study (scale bar: 100 µm).
Figure 7 Histological analysis of major healthy organs (heart, liver, spleen, lung, and kidney) at the end of efficacy study (scale bar: 100 µm).CC BY-NC · PubMed Central

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Metadata

Authors
Guo, X., Han, L., Chen, W., He, H., Zhang, W., Huang, C., & Wang, X.
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2024-01
Volume
Volume 19
Pages
247-261
ISSN
1178-2013
DOI
10.2147/ijn.s432407
PMC
PMC10790668
Cited by
14
References
1
Language
en
Licence
creativecommons.org/licenses/by-nc/3.0/ (unspecified)

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