Oxaliplatin lipidated prodrug synergistically enhances the anti-colorectal cancer effect of IL12 mRNA.
Drug Deliv Transl Res
; 14(11): 3186-3199, 2024 Nov.
Article
en En
| MEDLINE
| ID: mdl-38457025
ABSTRACT
Colorectal cancer (CRC) is the fourth most common cancer in the world, with the second highest incidence rate after lung cancer. Oxaliplatin (OXA) is a broad-spectrum anti-tumor agent with significant therapeutic efficacy in colorectal cancer, and as a divalent platinum analog, it is not selective in its distribution in the body and has systemic toxicity with continued use. Interleukin-12 (IL12) is an immunostimulatory cytokine with cytokine monotherapy that has made advances in the fight against cancer, limiting the clinical use of cytokines due to severe toxicity. Here, we introduced a long alkyl chain and N-methyl-2,2-diaminodiethylamine to the ligand of OXA to obtain OXA-LIP, which effectively reduces its toxicity and improves the uptake of the drug by tumor cells. We successfully constructed IL12 mRNA and used LNPs to deliver IL12 mRNA, and in vivo pharmacodynamic studies demonstrated that OXA-LIP combined with IL12 mRNA had better tumor inhibition and higher biosafety. In addition, it was investigated by pharmacokinetic experiments that the OXA-LIP drug could accumulate in nude mice at the tumor site, which prolonged the half-life and enhanced the anti-tumor efficiency of OXA. It is hoped that these results will provide an important reference for the subsequent research and development of OXA-LIP with IL12 mRNA, as well as provide new therapeutic approaches for the treatment of colon cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Mensajero
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Profármacos
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Neoplasias Colorrectales
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Interleucina-12
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Oxaliplatino
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Ratones Desnudos
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Drug Deliv Transl Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos