Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization DOI Open Access
Omotola D. Gbadegesin, Simeon K. Adesina

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2798 - 2798

Published: March 20, 2025

Combination chemotherapy is preferred for the treatment of ovarian cancer (OC). Systemic toxicity, however, frequently limits effectiveness treatment. Polymer–drug conjugates (PDCs) containing synergistic combinations chemotherapeutic drugs can be used to enhance therapeutic efficacy. We earlier reported use a strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC)-mediated polymerization method preparation single-drug PDCs. In this report, was prepare gemcitabine–doxorubicin combination PDC. The PDC had high molecular weight (Mw 1360 kDa) and drug loading (36.6% gemcitabine; 7.0% doxorubicin). It demonstrated cathepsin B-catalyzed release at pH 5.0 good hydrolytic stability 7.4. index analysis free gemcitabine doxorubicin showed concentration-dependent synergism (combination < 1) in OVCAR-3 OC cells. Compared individual (the concentration that inhibited 50% growth (IC50) > 50 µg/mL) (IC50 = 1.79 µg/mL), 0.99 greater cytotoxicity against cells less cytotoxic than equivalent 0.11 µg/mL). promising targeted OC.

Language: Английский

Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization DOI Open Access
Omotola D. Gbadegesin, Simeon K. Adesina

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2798 - 2798

Published: March 20, 2025

Combination chemotherapy is preferred for the treatment of ovarian cancer (OC). Systemic toxicity, however, frequently limits effectiveness treatment. Polymer–drug conjugates (PDCs) containing synergistic combinations chemotherapeutic drugs can be used to enhance therapeutic efficacy. We earlier reported use a strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC)-mediated polymerization method preparation single-drug PDCs. In this report, was prepare gemcitabine–doxorubicin combination PDC. The PDC had high molecular weight (Mw 1360 kDa) and drug loading (36.6% gemcitabine; 7.0% doxorubicin). It demonstrated cathepsin B-catalyzed release at pH 5.0 good hydrolytic stability 7.4. index analysis free gemcitabine doxorubicin showed concentration-dependent synergism (combination < 1) in OVCAR-3 OC cells. Compared individual (the concentration that inhibited 50% growth (IC50) > 50 µg/mL) (IC50 = 1.79 µg/mL), 0.99 greater cytotoxicity against cells less cytotoxic than equivalent 0.11 µg/mL). promising targeted OC.

Language: Английский

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