Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
Abstract
:1. Introduction
2. Results
2.1. Characterization of HSA–CDDP
2.2. Cytotoxic Effect of HSA–CDDP In Vitro
2.3. Antitumor Effect of HSA–CDDP In Vivo
2.4. Biodistribution of HSA–CDDP In Vivo
2.5. Biosafety of HSA–CDDP In Vivo
3. Discussion
4. Materials and Methods
4.1. Cell Lines
4.2. Preparation of CDDP Conjugated HSA
4.3. Conjugation of Fluorescence Dye to HSA and HSA–CDDP
4.4. Confocal Microscopy Imaging for Cellular Uptake of FNR648-HSA–CDDP
4.5. Cellular Cytotoxicity Studies
4.6. Cell Apoptosis Study
4.7. Animal Xenografts Tumor Model and Anti-Tumor Effect In Vivo
4.8. Biodistribution of CDDP Using ICP-MS
4.9. Hematology Analysis
4.10. Histopathology Examination
4.11. Serum Stability of HSA–CDDP
4.12. SPECT Imaging
4.13. Immunohistochemistry and TUNEL Assay
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CDDP | Cis-diamminedichloroplatinum (II) |
HSA | Human serum albumin |
SPARC | Secreted protein acidic and rich in cysteine |
EPR | Enhanced permeability and retention |
MALDI-TOF | Matrix-assisted laser desorption/ionization-time of flight |
CCK-8 | Cell counting kit-8 |
PBS | Phosphate buffered saline |
ICP-MS | Inductively coupled plasma-mass spectrometry |
%ID | Percent injected dose |
AST | Aspartate transaminase |
ALT | Alanine aminotransferase |
BUN | Blood urea nitrogen |
H&E | Hematoxylin-eosin |
TUNEL | Terminal deoxynucleotidyl transferase |
SPECT | Single photon emission computed tomography |
OCT2 | Organic cation transporter-2 |
ROS | Reactive oxygen species |
BBB | Blood–brain barrier |
MEM | Minimum essential medium |
FBS | Fetal bovine serum |
BCA | Bicinchoninic acid |
DBCO | Dibenzocyclooctyne |
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IC50 (μM) | U87MG | U87MG-shSPARC |
---|---|---|
CDDP | 2.545 ± 0.1345 | 2.646 ± 0.1302 |
HSA–CDDP | 11.49 ± 0.1726 | ≈59.3 |
Median Survival (Days) | PBS | CDDP | HSA–CDDP |
---|---|---|---|
U87MG | 12 | 22 | 20 |
U87MG-shSPARC | 30 | 42 | 32 |
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Park, C.R.; Kim, H.Y.; Song, M.G.; Lee, Y.-S.; Youn, H.; Chung, J.-K.; Cheon, G.J.; Kang, K.W. Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models. Int. J. Mol. Sci. 2020, 21, 7932. https://doi.org/10.3390/ijms21217932
Park CR, Kim HY, Song MG, Lee Y-S, Youn H, Chung J-K, Cheon GJ, Kang KW. Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models. International Journal of Molecular Sciences. 2020; 21(21):7932. https://doi.org/10.3390/ijms21217932
Chicago/Turabian StylePark, Cho Rong, Hyo Young Kim, Myung Geun Song, Yun-Sang Lee, Hyewon Youn, June-Key Chung, Gi Jeong Cheon, and Keon Wook Kang. 2020. "Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models" International Journal of Molecular Sciences 21, no. 21: 7932. https://doi.org/10.3390/ijms21217932