title: Redox-Activated Light-Up Nanomicelle for Precise Imaging-Guided Cancer Therapy and Real-Time Pharmacokinetic Monitoring.
abstract: Simultaneous tumor imaging, therapy, and pharmacokinetic monitoring can offer a safe and effective strategy for cancer therapy. This work describes the design of a fluorescence light-up nanomicelle that can afford precise imaging-guided drug delivery and pharmacokinetic monitoring in a real-time fashion for cancer chemotherapy. The nanomicelle, which contains a boron dipyrromethene based fluorescent probe as the hydrophobic core and a redox-triggered detachable poly(ethylene glycol) (PEG) shell, can accumulate at the tumor site via enhanced permeation and retention effect. The PEG detachment induced by tumoral and intracellular glutathione can destabilize the nanomicelle, leading to fluorescence light up and simultaneous drug release. Importantly, the fluorescence intensities generated by the nanomicelles in different organs are well-correlated with released drug concentrations in both temporal and spatial manners, suggesting its precise role for imaging-guided drug delivery and pharmacokinetic monitoring in vivo. The tumor growth can be effectively inhibited by the docetaxel-loaded nanomicelle formulation, and the nanomicelles are monitored to be excreted via hepatobiliary routes. This nanomicelle for precise imaging-guided chemotherapy provides a safe and robust theranostic strategy for the evaluation of cancer nanomedicine.
authors.affiliation: Department of Chemistry, Zhejiang University , Hangzhou 310028, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Zhejiang University , Hangzhou 310028, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology , Hangzhou 310032, China.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University , Hangzhou 310028, China.
authors.forename: Hongzhen
authors.identifier: 0000-0002-0886-3906
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Chemistry, Zhejiang University , Hangzhou 310028, China.
authors.forename: Shuoqing
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Bionanoengineering and State Key Laboratory for Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University , Hangzhou 310027, China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Chemistry, Zhejiang University , Hangzhou 310028, China.
authors.forename: Guping
authors.identifier: 0000-0003-3256-740X
authors.initials: G
authors.lastname: Tang
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University , Singapore 639798.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ping
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D008823:Micelles; D049329:Nanostructures; D009369:Neoplasms / Q000628:therapy*; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols
chemical_list: D008823:Micelles; D011092:Polyethylene Glycols
keywords: BODIPY; drug delivery; fluorescence imaging; reduction-sensitive polymer; theranostic nanomaterials