Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization
Abstract
1. Introduction
2. Results and Discussion
2.1. Synthesis and Characterization of P-Gem/Dox
2.2. In Vitro Cathepsin B-Catalyzed Cleavage of P-Gem/Dox
2.3. Hydrolytic Stability of P-Gem/Dox
2.4. In Vitro Cytotoxicity Evaluation
2.4.1. Cytotoxicity Evaluation of p-Dox
2.4.2. Cytotoxicity Evaluation of p-Gem
2.4.3. Cytotoxicity Evaluation of the Combination PDCs
2.4.4. Combination Index Analysis
3. Materials and Method
3.1. Materials
3.2. Synthesis of Gemcitabine–Doxorubicin Combination PDC (P-Gem/Dox)
3.3. Molecular Weight Characterization
3.4. Drug Content Evaluation
3.5. In Vitro Cathepsin B-Catalyzed Cleavage
3.6. In Vitro Hydrolytic Stability
3.7. In Vitro Cytotoxicity Evaluation in OVCAR-3 Cell Line
3.7.1. Cell Culture
3.7.2. Cytotoxicity Evaluation of the Single Agents
3.7.3. The Cytotoxicity Evaluation of the Combination Agents and Combination Index Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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PDCs | Mw (kDa) | Mn (kDa) | PdI | Mp (kDa) | % Weight Doxorubicin | % Weight Gemcitabine |
---|---|---|---|---|---|---|
p-Gem/Dox | 1360 | 1346.53 | 1.01 | 1240 | 7.00 ± 2.00 | 36.60 ± 0.24 |
p-Gem ø | 40.18 | 29.33 | 1.37 | 40.37 | Not applicable | 29.20 ± 0.30 |
p-Dox ø | 1800 | 1782.18 | 1.01 | 1920 | 10.30 ± 0.53 | Not applicable |
Drug Treatment | IC50 (µg/mL) |
---|---|
Single | |
p-Dox | 1.79 ± 0.17 |
Doxorubicin HCl (DOX) | 0.17 ± 0.03 |
p-Gem | >50 |
Gemcitabine HCl (GEM) | >50 |
Combination | |
p-Gem + p-Dox admixture (50:50) | 3.87 ± 1.22 |
GEM + DOX admixture (50:50) | 0.24 ± 0.12 |
p-Gem/Dox | 0.99 ± 0.06 |
GEM + DOX admixture (36.6:7) | 0.11 ± 0.04 |
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Gbadegesin, O.D.; Adesina, S.K. Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization. Int. J. Mol. Sci. 2025, 26, 2798. https://doi.org/10.3390/ijms26062798
Gbadegesin OD, Adesina SK. Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization. International Journal of Molecular Sciences. 2025; 26(6):2798. https://doi.org/10.3390/ijms26062798
Chicago/Turabian StyleGbadegesin, Omotola D., and Simeon K. Adesina. 2025. "Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization" International Journal of Molecular Sciences 26, no. 6: 2798. https://doi.org/10.3390/ijms26062798
APA StyleGbadegesin, O. D., & Adesina, S. K. (2025). Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization. International Journal of Molecular Sciences, 26(6), 2798. https://doi.org/10.3390/ijms26062798