title: Dual Functionalized Bacteriophage Qβ as a Photocaged Drug Carrier.
abstract: Proteinatious nanoparticles are emerging as promising materials in biomedical research owing to their many unique properties and our interest focuses on integrating environmental responsivity into these systems. In this work, the use of a virus-like particle (VLP) derived from bacteriophage Qβ as a photocaged drug delivery system is investigated. Ideally, a photocaged nanoparticle platform should be harmless and inert without activation by light yet, upon photoirradiation, should cause cell death. Approximately 530 photocleavable doxorubicin complexes are installed initially onto the surface of Qβ by CuAAC reaction for photocaging therapy; however, aggregation and precipitation are found to cause cell death at higher concentrations. In order to improve solution stability, thiol-dibromomaleimide chemistry has been developed to orthogonally modify the VLP. This chemistry provides a robust method of incorporating additional functionality at the disulfides on Qβ, which was used to increase the stability and solubility of the drug-loaded VLPs. As a result, the dual functionalied VLPs with polyethylene glycol and photocaged doxorubicin show not only negligible cytotoxicity before photoactivation but also highly controllable photorelease and cell killing power.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 West Campbell Road, Richardson, TX, 75080-3021, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 West Campbell Road, Richardson, TX, 75080-3021, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 West Campbell Road, Richardson, TX, 75080-3021, USA.
authors.forename: Luxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 West Campbell Road, Richardson, TX, 75080-3021, USA.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 West Campbell Road, Richardson, TX, 75080-3021, USA.
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Gassensmith
mesh_terms: D017908:Allolevivirus / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D019793:Fluorescein / Q000737:chemistry; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D008301:Maleimides / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry; D014771:Virion / Q000737:chemistry
chemical_list: C000625049:2,3-dibromomaleimide; D004220:Disulfides; D004337:Drug Carriers; D008301:Maleimides; D014764:Viral Proteins; D004317:Doxorubicin; D019793:Fluorescein
keywords: controlled drug release; orthogonal bioconjugation; protein-based nanoparticles