Increased Enzyme Loading in PICsomes via Controlling Membrane Permeability Improves Enzyme Prodrug Cancer Therapy Outcome
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Protein Expression and Purification
2.3. Material Characterization
2.4. Cell Lines and Animals
2.5. Preparation of CD@PICsomes
2.6. Preparation of Fluorescence Modified CD-Loaded PICsomes
2.7. Interaction of Pre-CL PICsomes and CD
2.8. Evaluation of Stability of CD@PICsome Based on Enzyme Activity Assay
2.9. Evaluation of In Vitro Cytotoxicity
2.10. Evaluation of Plasma Clearance and Biodistribution and Hepatotoxicity of CD@PICsome
2.11. Evaluation of In Vivo Therapeutic Effect
2.12. Statistical Analysis
3. Results and Discussion
3.1. Preparation of Crosslinked PICsomes Loaded with CD (CD@PICsomes) by SWCL
3.2. Interaction of Pre-CL PICsomes and CD
3.3. Stability of CD@PICsome Based on Enzyme Activity
3.4. Evaluation of Cytotoxicity of CD@PICsome
3.5. Evaluation of Plasma Clearance, Biodistribution, and Hepatotoxicity of CD@PICsome
3.6. Evaluation of In Vivo Therapeutic Effect of CD@PICsome
4. Conclusions
5. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample | Contents | ||
---|---|---|---|
CD@PICsome | 5-FC | 5-FU | |
1 | + | − | − |
2 | − | + (2 μg/mL) | − |
3 | − | + (4 μg/mL) | − |
4 | + | + (2 μg/mL) | − |
5 | + | + (4 μg/mL) | − |
6 | − | − | + (2 μg/mL) |
7 | − | − | + (4 μg/mL) |
8 | − | − | − |
Group | Day | ||||
---|---|---|---|---|---|
1 | 4 | 8 | 11 | 15 | |
1 | × | ♦ | ♦ | ♦ | ♦ |
2 | × | ◊ | ◊ | ◊ | ◊ |
3 | − | ■ | ■ | ■ | ■ |
4 | − | □ | □ | □ | □ |
5 | × | − | − | − | − |
6 | − | ♦ | ♦ | ♦ | ♦ |
7 | − | ◊ | ◊ | ◊ | ◊ |
8 | ∆ | ∆ | ∆ | ∆ | ∆ |
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Goto, A.; Anraku, Y.; Fukushima, S.; Kishimura, A. Increased Enzyme Loading in PICsomes via Controlling Membrane Permeability Improves Enzyme Prodrug Cancer Therapy Outcome. Polymers 2023, 15, 1368. https://doi.org/10.3390/polym15061368
Goto A, Anraku Y, Fukushima S, Kishimura A. Increased Enzyme Loading in PICsomes via Controlling Membrane Permeability Improves Enzyme Prodrug Cancer Therapy Outcome. Polymers. 2023; 15(6):1368. https://doi.org/10.3390/polym15061368
Chicago/Turabian StyleGoto, Akinori, Yasutaka Anraku, Shigeto Fukushima, and Akihiro Kishimura. 2023. "Increased Enzyme Loading in PICsomes via Controlling Membrane Permeability Improves Enzyme Prodrug Cancer Therapy Outcome" Polymers 15, no. 6: 1368. https://doi.org/10.3390/polym15061368