PUBLICATION
Enhanced antitumor activity and mechanism of biodegradable polymeric micelles-encapsulated chetomin in both transgenic zebrafish and mouse models
- Authors
- Wu, Q., Li, G., Deng, S., Ouyang, L., Li, L., Liu, L., Luo, N., Song, X., He, G., Gong, C., Wei, Y.
- ID
- ZDB-PUB-140903-14
- Date
- 2014
- Source
- Nanoscale 6(20): 11940-52 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents/chemistry*
- Apoptosis
- Biocompatible Materials/chemistry*
- Disease Models, Animal
- Disulfides/chemistry*
- Fermentation
- Glutathione/chemistry
- Hydrogels/chemistry
- Indole Alkaloids/chemistry*
- Mice
- Micelles*
- Microcirculation
- Models, Molecular
- Molecular Dynamics Simulation
- Neoplasm Metastasis
- Neoplasms/drug therapy
- Particle Size
- Polyethylene Glycols/chemistry
- Polymers/chemistry*
- Reactive Oxygen Species/chemistry
- Temperature
- Zebrafish
- PubMed
- 25175172 Full text @ Nanoscale
Citation
Wu, Q., Li, G., Deng, S., Ouyang, L., Li, L., Liu, L., Luo, N., Song, X., He, G., Gong, C., Wei, Y. (2014) Enhanced antitumor activity and mechanism of biodegradable polymeric micelles-encapsulated chetomin in both transgenic zebrafish and mouse models. Nanoscale. 6(20):11940-52.
Abstract
Chetomin is a promising molecule with anti-tumor activities in the epipolythiodioxopiperazine family of fungal secondary metabolites; however, strong hydrophobicity has limited its further applications. In this work, chetomin was encapsulated into polymeric micelles to obtain an aqueous formulation, and the chetomin loaded micelles (Che-M) exhibited small particle size and high encapsulation efficiency. When the concentration of copolymer was higher than the critical gelation concentration, the Che-M could form a thermosensitive hydrogel (Che-H), which was free-flowing sol at ambient temperature and converted into a non-flowing gel at body temperature. The molecular modeling study has indicated that chetomin interacted with PCL as a core, which was embraced by PEG as a shell. Che-M showed equal cytotoxicity with free chetomin, but the apoptosis inducing effects of Che-M were more significant. Besides, Che-M could increase the GSSG level, decrease the GSH level, and increase the ROS in CT26 cells. Furthermore, stronger inhibitory effects of Che-M were observed on embryonic angiogenesis, tumor-induced angiogenesis and tumor growth in transgenic zebrafish models. In addition, Che-M was effective in inhibiting tumor growth and prolonging survival in a subcutaneous CT26 tumor model. In a colorectal peritoneal carcinomatosis model, both Che-M and Che-H showed excellent therapeutic effects, but Che-H was more effective. In conclusion, Che-M and Che-H may serve as candidates for cancer therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping