title: Supramolecular adducts of squaraine and protein for noninvasive tumor imaging and photothermal therapy in vivo.
abstract: Extensive efforts have been devoted to the development of near-infrared (NIR) dye-based imaging probes and/or photothermal agents for cancer theranostics in vivo. However, the intrinsic chemical instability and self-aggregation properties of NIR dyes in physiological condition limit their widely applications in the pre-clinic study in living animals. Squaraine dyes are among the most promising NIR fluorophores with high absorption coefficiencies, bright fluorescence and photostability. By introducing dicyanovinyl groups into conventional squaraine (SQ) skeleton. These acceptor-substituted SQ dyes not only show superior NIR fluorescence properties (longer wavelength, higher quantum yield) but also exhibit more chemical robustness. In this work, we demonstrated highly stable and biocompatible supramolecular adducts of SQ and the natural carrier protein, i.e., bovine serum albumin (BSA) (SQ⊂BSA) for tumor targeted imaging and photothermal therapy in vivo. SQ was selectively bound to BSA hydrophobic domain via hydrophobic and hydrogen bonding interactions with up to 80-fold enhanced fluorescence intensity. By covalently conjugating target ligands to BSA, the SQ⊂BSA was capable of targeting tumor sites and allowed for monitoring the time-dependent biodistribution of SQ⊂BSA, which consequently determined the protocol of photothermal therapy in vivo. We envision that this supramolecular strategy for selectively binding functional imaging agents and/or drugs into human serum albumin might potentially utilize in the preclinical and even clinic studies in the future.
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, 19 B, Yuquan Road, Beijing, China.
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Gao
authors.forename: Yao-Xin
authors.initials: YX
authors.lastname: Lin
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Li
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mayerhöffer
authors.forename: Peter
authors.initials: P
authors.lastname: Spenst
authors.forename: Ji-Guo
authors.initials: JG
authors.lastname: Su
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Li
authors.forename: Frank
authors.initials: F
authors.lastname: Würthner
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D003503:Cyclobutanes / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D061848:Optical Imaging; D010636:Phenols / Q000737:chemistry / Q000627:therapeutic use*; D010789:Phototherapy; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D003503:Cyclobutanes; D005456:Fluorescent Dyes; D010636:Phenols; C480596:squaraine; D012710:Serum Albumin, Bovine
keywords: Near-infrared imaging; Photothermal therapy; Serum albumin; Squaraines; Supramolecular