title: Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumor-targeted drug delivery and positron emission tomography imaging.
abstract: Brush-shaped amphiphilic block copolymers were conjugated with a monoclonal antibody against CD105 (i.e., TRC105) and a macrocyclic chelator for (64)Cu-labeling to generate multifunctional theranostic unimolecular micelles. The backbone of the brush-shaped amphiphilic block copolymer was poly(2-hydroxyethyl methacrylate) (PHEMA) and the side chains were poly(L-lactide)-poly(ethylene glycol) (PLLA-PEG). The doxorubicin (DOX)-loaded unimolecular micelles showed a pH-dependent drug release profile and a uniform size distribution. A significantly higher cellular uptake of TRC105-conjugated micelles was observed in CD105-positive human umbilical vein endothelial cells (HUVEC) than nontargeted micelles due to CD105-mediated endocytosis. In contrast, similar and extremely low cellular uptake of both targeted and nontargeted micelles was observed in MCF-7 human breast cancer cells (CD105-negative). The difference between the in vivo tumor accumulation of (64)Cu-labeled TRC105-conjugated micelles and that of nontargeted micelles was studied in 4T1 murine breast tumor-bearing mice, by serial positron emission tomography (PET) imaging and validated by biodistribution studies. These multifunctional unimolecular micelles offer pH-responsive drug release, noninvasive PET imaging capability, together with both passive and active tumor-targeting abilities, thus making them a desirable nanoplatform for cancer theranostics.
authors.affiliation: School of Chemical Engineering, Tianjin University , Tianjin 300072, China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Guo
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.forename: Sixiang
authors.initials: S
authors.lastname: Shi
authors.forename: Tapas R
authors.initials: TR
authors.lastname: Nayak
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007773:Lactates / Q000737:chemistry; D061986:MCF-7 Cells; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D011102:Polyhydroxyethyl Methacrylate / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011247:Pregnancy; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; D011108:Polymers; C088513:poly(lactic acid-ethylene glycol); D011102:Polyhydroxyethyl Methacrylate; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: 64Cu; CD105; angiogenesis; brush polymer; brush-shaped amphiphilic block copolymer; cancer; nanocarriers; positron emission tomography (PET); theranostics; unimolecular micelles