Multitargeting Prodrugs that Release Oxaliplatin, Doxorubicin and Gemcitabine are Potent Inhibitors of Tumor Growth and Effective Inducers of Immunogenic Cell Death

0577353 - BFÚ 2024 RIV DE eng J - Journal Article
Sarkar, A. - Novohradský, Vojtěch - Maji, M. - Babu, T. - Marková, Lenka - Kostrhunová, Hana - Kašpárková, Jana - Gandin, V. - Brabec, Viktor - Gibson, D.
Multitargeting Prodrugs that Release Oxaliplatin, Doxorubicin and Gemcitabine are Potent Inhibitors of Tumor Growth and Effective Inducers of Immunogenic Cell Death.
Angewandte Chemie - International Edition. Roč. 62, č. 42 (2023). ISSN 1433-7851. E-ISSN 1521-3773
R&D Projects: GA ČR(CZ) GA23-06307S
Institutional support: RVO:68081707
Keywords : Doxorubicin * Gemcitabine * Immunogenic Cell Death * Multi-Targeting Prodrugs * Oxaliplatin
OECD category: Immunology
Impact factor: 16.6, year: 2022
Method of publishing: Open access
https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202310774

A multitargeting prodrug (2) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent with nM IC50s, it is highly selective to cancer cells with mean selectivity indices to human (136) and murine (320) cancer cells. It effectively induces release of DAMPs (CALR, ATP & HMGB1) in CT26 cells facilitating more efficient phagocytosis by J774 macrophages than the FDA drugs or their co-administration. The viability of CT26 cells co-cultured with J774 macrophages and treated with 2 was reduced by 32 % compared to the non-treated cells, suggesting a synergistic antiproliferative effect between the chemical and immune reactions. 2 inhibited in vivo tumor growth in two murine models (LLC and CT26) better than the FDA drugs or their co-administration with significantly lower body weight loss. Mice inoculated with CT26 cells treated with 2 showed slightly better tumor free survival than doxorubicin.
Permanent Link: https://hdl.handle.net/11104/0349137