Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation and Characterization of Gemcitabine and Paclitaxel (GT) in Drug Combination Nanoparticles
2.3. Preparation of Freely and Soluble Gemcitabine and Paclitaxel (GT) Combination
2.4. Development and Characterization of 4T1 Breast Tumor in Mouse Mammary Fat Pads
2.5. Immunohistochemistry (IHC) Staining of CD31 and Podoplanin to Detect Developing Tumor Blood and Lymphatic Vasculature
2.6. Comparison of Tumor Inhibition Effects of Equivalent Doses of Gemcitabine and Paclitaxel in DcNP or Free Form
2.7. Dose Dependence of Gemcitabine and Paclitaxel in DcNP on Tumor Growth Inhibition
2.8. Time Course of Gemcitabine and Paclitaxel (GT) in Tumors and Plasma in 4T1 Tumor Bearing Mouse Model and Biodistribution Study
2.9. Extraction of Drugs from Plasma and Tissues
2.10. Quantification of Gemcitabine and Paclitaxel in Plasma and Tumors by HPLC-MS/MS
2.11. Effect of GT-in-DcNP on Human MDA-231-HM Tumor Implanted in Fat-Pad of Athymic Mice
2.12. Statistical Analysis
3. Results
3.1. Characterization of a Primary Multi-Site Mammary Fat Pad 4T1 Breast Cancer Model
3.2. Characterization of Lymph and Blood Vasculature Development in Primary 4T1 Tumors
3.3. Effects of DcNP on Gemcitabine and Paclitaxel Combination to Inhibit 4T1 Mammary Tumor
3.4. Dose–Response Study of Gemcitabine and Paclitaxel in DcNP Form to Suppress 4T1 Breast Tumor
3.5. Mechanisms Relating to DcNP Mediated Enhancement in GT Exposure Leading to 4T1 Mammary Tumor Regression and Inhibition
3.5.1. Effects of Drug Combination Nanoparticles on Gemcitabine and Paclitaxel Transit and Accumulation in Lymphatic Vessels and Tumors
3.5.2. Ability of DcNP to Enhance Gemcitabine and Paclitaxel Retention in Tumors and Extend Persistence of Plasma Drug Concentrations
3.6. Safety and Pathology of DcNP Effects on GT Drug Combination Treatment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
G | Gemcitabine |
T | Paclitaxel |
DcNP | Drug combination nanoparticles |
IV | Intravenous/intravenously |
SC | Subcutaneous/subcutaneously |
DSPC | 1,2-distearoyl-sn-glycero-3-phosphocholine |
DSPE-mPEG2000 | 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] |
ICG | Indocyanine green |
GFP | Green fluorescence protein |
IVIS | In vivo imaging system |
IHC | Immunohistochemistry |
AE% | Association efficiency |
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Cell Number | Volume | # of Tumors | Live Tumor Luminescence (Photon Counts) b | Tumor Volume at Day 5 (mm3) a | ||
---|---|---|---|---|---|---|
(Million) | Inoculant (µL) | Day 1 | Day 3 | Tumor Growth (Fold-Change) | ||
0.2 | 20 | 4 | 760 ± 894 | 7769 ± 6975 | 10.2 | N/A d |
0.5 | 50 | 4 | 2617 ± 3294 | 14,759 ± 17,201 | 5.6 | N/A d |
1 | 100 c | 4 | 4350 ± 995 | 23,435 ± 11,180 | 5.4 | N/A d |
1 | 50 | 12 | 3244 ± 1942 | 16,021 ± 13,247 | 4.9 | 40 ± 17 |
1 | 50 | 16 | 1386 ± 1950 | 8389 ± 9889 | 6 | 53 ± 44 |
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Yu, J.; Xu, X.; Griffin, J.I.; Mu, Q.; Ho, R.J.Y. Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression. Cancers 2024, 16, 2792. https://doi.org/10.3390/cancers16162792
Yu J, Xu X, Griffin JI, Mu Q, Ho RJY. Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression. Cancers. 2024; 16(16):2792. https://doi.org/10.3390/cancers16162792
Chicago/Turabian StyleYu, Jesse, Xiaolin Xu, James Ian Griffin, Qingxin Mu, and Rodney J. Y. Ho. 2024. "Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression" Cancers 16, no. 16: 2792. https://doi.org/10.3390/cancers16162792
APA StyleYu, J., Xu, X., Griffin, J. I., Mu, Q., & Ho, R. J. Y. (2024). Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression. Cancers, 16(16), 2792. https://doi.org/10.3390/cancers16162792