title: Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.
abstract: Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Feirong
authors.initials: F
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, School of Biotechnology, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University , Qingdao 266003, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University , Qingdao 266003, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Ning
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, School of Biotechnology, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University , Qingdao 266003, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Materials Science and Engineering, The University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Shanfeng
authors.identifier: 0000-0001-9790-5970
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000737:chemistry; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy*; D051379:Mice; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007783:Lactones; D011091:Polyesters; D011108:Polymers; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D003474:Curcumin
keywords: antitumor; blood-stable; curcumin; polymer micelles