Abstract | BACKGROUND: METHODS: The cytotoxicity of BU-loaded micelles against drug-resistant colon cancer LoVo/ADR and HCT116/LOHP cells was measured by CCK-8 assay. The cellular uptake, Rho123 accumulation, and cell apoptosis were determined by flow cytometry. The expression of apoptosis-related protein and P-gp was measured by Western blot assay. The antitumor activity of BU-loaded micelles was evaluated in LoVo/ADR-bearing nude mice. RESULTS: BU-loaded VES-CSO/ TPGS-RGD mixed micelles (BU@VeC/T-RGD MM) were 140.3 nm in diameter with zeta potential of 8.66 mV. The BU@VeC/T-RGD MM exhibited good stability, sustained-release pattern, higher intracellular uptake, and greater cytotoxicity in LoVo/ADR cells. Furthermore, the mechanisms of the BU@VeC/T-RGD MM to overcome MDR might be due to enhanced apoptosis rate and P-gp efflux inhibition. Subsequently, in vivo studies confirmed an enhanced therapeutic efficiency and reduced side effects associated with BU@VeC/T-RGD MM compared with free BU, owing to the enhanced permeation and retention effect, improved pharmacokinetic behavior, and tumor targeting, which lead to MDR-inhibiting effect in LoVo/ADR-bearing nude mice. CONCLUSION: Our results demonstrated that VeC/T-RGD MM could be developed as a potential delivery system for BU to improve its antitumor activity against drug-resistant colon cancer.
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Authors | Zeting Yuan, Yuxia Yuan, Lin Han, Yanyan Qiu, Xiaqin Huang, Feng Gao, Guohua Fan, Yixi Zhang, Xueyao Tang, Xue He, Ke Xu, Peihao Yin |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 13
Pg. 7533-7548
( 2018)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 30532537
(Publication Type: Journal Article)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antineoplastic Agents
- Bufanolides
- Micelles
- Oligopeptides
- Oligosaccharides
- Vitamin E
- Rhodamine 123
- arginyl-glycyl-aspartic acid
- Doxorubicin
- Chitosan
- tocophersolan
- bufalin
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(metabolism)
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Bufanolides
(pharmacology, therapeutic use)
- Chitosan
(chemistry)
- Colonic Neoplasms
(drug therapy, pathology)
- Doxorubicin
(pharmacology, therapeutic use)
- Drug Resistance, Neoplasm
- HCT116 Cells
- Humans
- Mice, Nude
- Micelles
- Oligopeptides
(chemistry)
- Oligosaccharides
(chemistry)
- Rhodamine 123
(metabolism)
- Tumor Burden
- Vitamin E
(chemistry)
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