Dataset Information

Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles.

ABSTRACT: Hepatic metastasis is the leading cause of mortality of colon cancer, which is still lack of an effective therapy. A new delivery system, pluronic P85 block copolymers, conveying chemotherapeutic agent 5-fluorouracil (5-Fu) for inhibiting growth and metastasis of colon cancer was designed and developed. In this study, we demonstrated that 5-Fu produce strong pesticide effect at lower doses in the present of pluronic P85 compared with control groups. The migration and invasion of HCT116 cells and RKO cells were examined and the results showed that migration and invasion capacities of HCT116 cells and RKO cells were reduced by administering 5-Fu/P85 copolymer micelles in vitro and in vivo which indicating an effectively activity. Interestingly, the content of CD133?+?CXCR4+ cells in HCT116 cancer cells and RKO cells treated by 5-Fu/P85 copolymer micelles was decreased. Importantly, the epithelial-mesenchymal transition (EMT) of CD133?+?CXCR4+ cells, which was strongly associated with liver metastasis of colon cancer, was also suppressed by giving 5-Fu/P85 copolymer micelles. The results indicated that 5-Fu/P85 copolymer micelles could inhibit the growth and metastasis of colon cancer, which could be attributed to the decrease of the content of CD133?+?CXCR4+ cells and suppression of EMT of CD133?+?CXCR4+ cells.

SUBMITTER: Zhu P

PROVIDER: S-EPMC4750032 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles.

Zhu Pengxi P Zhao Naping N Sheng Dandan D Hou Jing J Hao Chong C Yang Xue X Zhu Bing B Zhang Shanshan S Han Zhipeng Z Wei Lixin L Zhang Li L

Scientific reports 20160211

Hepatic metastasis is the leading cause of mortality of colon cancer, which is still lack of an effective therapy. A new delivery system, pluronic P85 block copolymers, conveying chemotherapeutic agent 5-fluorouracil (5-Fu) for inhibiting growth and metastasis of colon cancer was designed and developed. In this study, we demonstrated that 5-Fu produce strong pesticide effect at lower doses in the present of pluronic P85 compared with control groups. The migration and invasion of HCT116 cells and ...[more]

PMID: 26864651

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Project description:Here, we developed Pluronic® P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB-VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori.

Dataset Information

Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles.

Publications

Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles.

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