title: Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy.
abstract: When designing drug carriers, the drug-to-carrier ratio is an important consideration, because the use of high quantities of carriers can result in toxicity as a consequence of poor metabolism and elimination of the carriers. However, these issues would be of less concern if both the drug and carrier had therapeutic effects. (-)-Epigallocatechin-3-O-gallate (EGCG), a major ingredient of green tea, has been shown, for example, to possess anticancer effects, anti-HIV effects, neuroprotective effects and DNA-protective effects. Here, we show that sequential self-assembly of the EGCG derivative with anticancer proteins leads to the formation of stable micellar nanocomplexes, which have greater anticancer effects in vitro and in vivo than the free protein. The micellar nanocomplex is obtained by complexation of oligomerized EGCG with the anticancer protein Herceptin to form the core, followed by complexation of poly(ethylene glycol)-EGCG to form the shell. When injected into mice, the Herceptin-loaded micellar nanocomplex demonstrates better tumour selectivity and growth reduction, as well as longer blood half-life, than free Herceptin.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Joo Eun
authors.initials: JE
authors.lastname: Chung
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Susi
authors.initials: S
authors.lastname: Tan
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Shu Jun
authors.initials: SJ
authors.lastname: Gao
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Nunnarpas
authors.initials: N
authors.lastname: Yongvongsoontorn
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215 USA.
authors.forename: Soon Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215 USA.
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215 USA.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.|Department of Pathology, Kurume University School of Medicine, Kurume University, 67 Asahi-machi, 830-0011 Kurume, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Motoichi
authors.initials: M
authors.lastname: Kurisawa
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669 Singapore.
authors.forename: Jackie Y
authors.initials: JY
authors.lastname: Ying
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D002392:Catechin; C045651:epigallocatechin gallate; D000068878:Trastuzumab