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Triphenylphosphonium-modified poly(ethylene glycol)-poly(epsilon-caprolactone) micelles for mitochondria- targeted gambogic acid delivery
Xu, Yingqi1; Wang, Shengpeng1; Chan, Hon Fai2; Liu, Yuling3; Li, Hui3; He, Chengwei1; Li, Zeyong4; Chen, Meiwan1
2017-04-30
Source PublicationINTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN0378-5173
Volume522Issue:1-2Pages:21-33
Abstract

Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(epsilon-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07 +/- 11.71 nm and an encapsulation efficiency of 80.78 +/- 1.36%, and they displayed homogeneous spherical shapes. The GA-TPP micelles exerted enhanced cytotoxic and pro-apoptotic effect against A549 cells compared to free GA and GA-loaded PEG-PCL (GA-PP) micelles, due to the inhibition of the expression of apoptosis-related proteins and promotion of caspase 3/7 and caspase 9 activity. Notably, the mitochondria-targeting GA-TPP micelles selectively accumulated in the mitochondria, inducing the loss of mitochondrial membrane potential and the release of cytochrome c, thereby achieving improved mitochondria-targeting effects. In conclusion, the GA-TPP micelle system shows great promise for lung cancer treatment by inducing an apoptotic effect via the mitochondria signaling pathway. (C) 2017 Elsevier B.V. All rights reserved.

KeywordGambogic Acid Polymeric Micelles Mitochondrial Targeting Lung Cancer
DOI10.1016/j.ijpharm.2017.01.064
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000400216700003
PublisherELSEVIER SCIENCE BV
The Source to ArticleWOS
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
2.Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
3.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
4.Department of Laboratory Medicine, Guangdong No. 2 Provincial People's Hospital, Guangzhou 510317, China.
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Xu, Yingqi,Wang, Shengpeng,Chan, Hon Fai,et al. Triphenylphosphonium-modified poly(ethylene glycol)-poly(epsilon-caprolactone) micelles for mitochondria- targeted gambogic acid delivery[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2017,522(1-2):21-33.
APA Xu, Yingqi.,Wang, Shengpeng.,Chan, Hon Fai.,Liu, Yuling.,Li, Hui.,...&Chen, Meiwan.(2017).Triphenylphosphonium-modified poly(ethylene glycol)-poly(epsilon-caprolactone) micelles for mitochondria- targeted gambogic acid delivery.INTERNATIONAL JOURNAL OF PHARMACEUTICS,522(1-2),21-33.
MLA Xu, Yingqi,et al."Triphenylphosphonium-modified poly(ethylene glycol)-poly(epsilon-caprolactone) micelles for mitochondria- targeted gambogic acid delivery".INTERNATIONAL JOURNAL OF PHARMACEUTICS 522.1-2(2017):21-33.
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