title: Triphenylphosphonium-modified poly(ethylene glycol)-poly(ε-caprolactone) micelles for mitochondria- targeted gambogic acid delivery.
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(ε-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±11.71nm 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 mitochondrial signaling pathway.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
authors.forename: Hon Fai
authors.initials: HF
authors.lastname: Chan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Laboratory Medicine, Guangdong No. 2 Provincial People's Hospital, Guangzhou 510317, China. Electronic address: sunnar78@126.com.
authors.forename: Zeyong
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China. Electronic address: mwchen@umac.mo.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008823:Micelles; D008928:Mitochondria / Q000187:drug effects*; D009861:Onium Compounds / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014320:Triphenylmethyl Compounds / Q000737:chemistry*; D044004:Xanthones / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D008823:Micelles; D009861:Onium Compounds; D011091:Polyesters; D014320:Triphenylmethyl Compounds; D044004:Xanthones; C011561:triphenylmethylphosphonium; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; C052659:gambogic acid; D045304:Cytochromes c; D020169:Caspases
keywords: Gambogic acid; Lung cancer; Mitochondrial targeting; Polymeric micelles