Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Animals
2.3. Synthesis of Ce6-Conjugated BSA (BSA-Ce6)
2.4. Preparation of ICG/PTX/BSA-Ce6-NPs
2.5. Fabrication of BSA-Stabilized PFC Nano-Emulsion
2.6. Characterization of ICG/PTX/BSA-Ce6-NPs and BSA-PFC-NEs
2.7. Preparation of In Situ-Gelling PEG Hydrogel with ICG/PTX/BSA-Ce6-NPs and BSA-PFC-NEs
2.8. Characterization of ICG/PTX/BSA-Ce6-NPs~PFC-NEs@Gel
2.9. In Vitro and In Vivo Photothermal Imaging and Hyperthermia Monitoring
2.10. Singlet Oxygen Generation by ICG/PTX/BSA-Ce6-NPs
2.11. Encapsulation Efficiency and Release Profiles of PTX, ICG, and BSA-Ce6
2.12. Cytotoxicity of ICG/PTX/BSA-Ce6-NPs in 4T1 Cell Spheroids Using LIVE/DEADTM Cell Assay
2.13. ROS Deep Assay at 4T1 Cell Spheroids
2.14. HIF-1α Visualization at 4T1 Cell Spheroids
2.15. In Vivo Imaging of ICG/PTX/BSA-Ce6-NPs
2.16. In Vivo Photoacoustic Imaging
2.17. In Vivo Antitumor Efficacy in 4T1 Cell-Xenograft Mice
2.18. Data Analyses
3. Results
3.1. Preparation and Characterization of ICG/PTX/BSA-Ce6-NPs and BSA-PFC-NEs
3.2. Preparation, Characterization, and Drug Release Profiles of ICG/PTX/BSA-Ce6-NPs~PFC-NEs@Gel
3.3. Photothermal and Photodynamic Activity of ICG/PTX/BSA-Ce6-NPs
3.4. Cytotoxicity Evaluation of 4T1 Cell Spheroids Based on LIVE/DEAD™ Assay
3.5. Visualization of Hypoxia in 4T1 Cell Spheroids
3.6. Visualization of Singlet Oxygen Generation in 4T1 Cell Spheroids
3.7. In Vivo Tumor Localization of ICG/PTX/BSA-Ce6-NPs~PFC-NEs@Gel in 4T1 Tumor-Bearing Mice
3.8. Photoacoustic Imaging of 4T1 Cell-Xenograft Tumors
3.9. Antitumor Efficacy in 4T1 Tumor-Bearing Mice
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Hydrogel Formulation Groups | Characteristics | Abbreviation | Laser Irradiation | Ultrasound |
---|---|---|---|---|
Z1 | PEG hydrogel | - | - | - |
Z2 | PEG hydrogel with PTX/BSA-NPs | PTX/BSA-NPs@Gel | - | - |
Z3 | PEG hydrogel with BSA-PFC-NEs | BSA-PFC-NEs@Gel | - | - |
Z4 | PEG hydrogel with PTX/BSA-Ce6-NPs | PTX/BSA-Ce6-NPs@Gel | - | - |
Z5 | PEG hydrogel with ICG/PTX-BSA-NPs | ICG/PTX-BSA-NPs@Gel | - | - |
Z6 | PEG hydrogel with ICG/PTX/BSA-Ce6-NPs and BSA-PFC-NEs | ICG/PTX/BSA-Ce6-NPs~PFC-NEs@Gel | - | - |
Animal Group | Intratumor Treatment Groups | Laser Irradiation | Ultrasound | |
G1 | PBS | - | - | - |
G2 | PEG hydrogel with PTX-BSA-NPs | PTX/BSA-NPs@Gel | - | - |
G3 | PEG hydrogel with ICG/PTX/BSA-Ce6-NPs | ICG/PTX/BSA-Ce6-NPs@Gel | 660 nm (+) | - |
G4 | 808 nm (+) | - | ||
G5 | PEG hydrogel with ICG/PTX/BSA-Ce6-NPs and BSA-PFC-NEs | ICG/PTX/BSA-Ce6-NPs~PFC-NEs@Gel | 660 nm/808 nm (+) | US (+) |
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Lee, W.T.; Yoon, J.; Kim, S.S.; Kim, H.; Nguyen, N.T.; Le, X.T.; Lee, E.S.; Oh, K.T.; Choi, H.-G.; Youn, Y.S. Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors. Pharmaceutics 2022, 14, 148. https://doi.org/10.3390/pharmaceutics14010148
Lee WT, Yoon J, Kim SS, Kim H, Nguyen NT, Le XT, Lee ES, Oh KT, Choi H-G, Youn YS. Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors. Pharmaceutics. 2022; 14(1):148. https://doi.org/10.3390/pharmaceutics14010148
Chicago/Turabian StyleLee, Woo Tak, Johyun Yoon, Sung Soo Kim, Hanju Kim, Nguyen Thi Nguyen, Xuan Thien Le, Eun Seong Lee, Kyung Taek Oh, Han-Gon Choi, and Yu Seok Youn. 2022. "Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors" Pharmaceutics 14, no. 1: 148. https://doi.org/10.3390/pharmaceutics14010148
APA StyleLee, W. T., Yoon, J., Kim, S. S., Kim, H., Nguyen, N. T., Le, X. T., Lee, E. S., Oh, K. T., Choi, H.-G., & Youn, Y. S. (2022). Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors. Pharmaceutics, 14(1), 148. https://doi.org/10.3390/pharmaceutics14010148