title: Reactive oxygen species-responsive protein modification and its intracellular delivery for targeted cancer therapy.
abstract: Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A-NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A-NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A-NBC reactivation, RNase A-NBC shows a significant specific cytotoxicity against tumor cells.
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA).
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Shuo
authors.initials: S
authors.lastname: Sun
authors.forename: Caleb I
authors.initials: CI
authors.lastname: Neufeld
authors.forename: Bernardo
authors.initials: B
authors.lastname: Perez-Ramirez
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Xu
mesh_terms: D001593:Benzyl Compounds / Q000737:chemistry* / Q000378:metabolism; D002254:Carbonates / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D057487:Enzyme Therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001593:Benzyl Compounds; D002254:Carbonates; D017382:Reactive Oxygen Species; D012259:Ribonuclease, Pancreatic
keywords: ROS-responsive; drug delivery; nanoparticles; protein engineering; targeted cancer therapy