Targeted low-dose TNFα delivered by TCP-1 peptide exerts differential synergistic effects on anti-cancer actions of chemotherapeutic drugs
| Autor: | Chi Hin Cho, Lin Zhang, Jing Shen, Lan Lu, Long Fei Li, Mingxing Li, Jian Hao Wang, Zhi Jie Li |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
business.industry Colorectal cancer Low dose Pharmaceutical Science Cancer Peptide Pharmacology medicine.disease Endothelial stem cell 03 medical and health sciences 0302 clinical medicine Therapeutic index chemistry 030220 oncology & carcinogenesis Medicine Tumor necrosis factor alpha Chemotherapeutic drugs business 030215 immunology |
| Zdroj: | Journal of Drug Delivery Science and Technology. 44:475-481 |
| ISSN: | 1773-2247 |
| DOI: | 10.1016/j.jddst.2018.02.009 |
| Popis: | Minute amounts of tumor vasculature-targeted TNFα was reported to increase endothelial permeability, thereby accelerating drug penetration and increasing the therapeutic index of chemotherapeutic agents. This study aimed at assessing the synergistic anti-cancer effects of three chemotherapeutic drugs and tumor vasculature-targeted TNFα in a murine orthotopic colorectal cancer model. TNFα was firstly coupled with a vascular-homing peptide TCP-1 to form a TNFα derivative (TCP-1/TNFα). After pretreated with 1 ng TCP-1/TNFα, the three chemotherapeutic drugs exerted differential synergistic effects on anti-cancer actions and presented different intratumoral accumulation statuses. To further assess transvascular transport efficiency of these drugs, an in vitro system was carried out to mimic the endothelial cell monolayer. Results showed that 5-fluorouracil which exerted the best anti-cancer action and intratumoral accumulation status with preadministration of 1 ng TCP-1/TNFα had the highest transvascular transportation efficiency. This work would provide important information for designing clinical studies with vasculature-targeted TNFα in combination with chemotherapeutic drugs for optimal synergism. |
| Databáze: | OpenAIRE |
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