title: Tetraphenylethene-based highly emissive metallacage as a component of theranostic supramolecular nanoparticles.
abstract: A theranostic agent combines diagnostic reporter with therapeutic activity in a single entity, an approach that seeks to increase the efficacy of cancer treatment. Herein, we describe the synthesis of a highly emissive tetraphenylethene-based metallacage using multicomponent coordination-driven self-assembly that exhibits a coordination-triggered aggregation-induced emission (AIE) enhancement. The formation of metallacage-loaded nanoparticles (MNPs) occurs when the assembly is treated with two variants of a 1,2-distearoyl-phosphatidylethanolamine (DSPE)/polyethylene glycol (PEG) conjugate, mPEG-DSPE, and biotin-PEG-DSPE. This combination endows the resultant MNPs with excellent stability and targeting ability, specifically enabling selective delivery of the metallacages to cancer cells that overexpress biotin receptors via receptor-mediated endocytosis. Although the mechanism of activity is based on existing Pt(II) anticancer drugs such as oxaliplatin, carboplatin, and cisplatin, in vitro and in vivo studies indicate that the MNPs are more active and show low systemic activity while also possessing emissive properties that allow for fluorescence-based imaging. This pioneering example of a metallacage that combines biologically active components with AIE imaging establishes supramolecular coordination complexes imbedded within nanoparticles as a promising potential theranostic platform for cancer treatment.
authors.affiliation: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance and Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Guocan
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Chemistry, University at Buffalo, State University of New York, 359 Natural Sciences Complex, Buffalo, NY 14260.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Cook
authors.affiliation: Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
authors.forename: Xuzhou
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance and Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Guping
authors.initials: G
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance and Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China; stang@chem.utah.edu fhuang@zju.edu.cn shawn.chen@nih.gov.
authors.forename: Feihe
authors.initials: F
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 stang@chem.utah.edu fhuang@zju.edu.cn shawn.chen@nih.gov.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112; stang@chem.utah.edu fhuang@zju.edu.cn shawn.chen@nih.gov.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stang
keywords: discrete metallacage; drug delivery; self-assembly; supramolecular coordination complex; theranostic