title: Design of Block Copolymer Micellar Aggregates for Co-Delivery of Enzyme and Anticancer Prodrug.
abstract: Traditional enzyme-prodrug therapy (EPT) is a two-step strategy, which has many serious deficiencies, so having a one-step EPT treatment becomes a problem of immediate interest. This study aims to achieve an effective co-delivery of horseradish peroxidase (HRP) as a kind of enzyme for prodrug activation and ethyl 3-indoleacetate (EIA) as anticancer prodrug. A ternary block copolymer PEG-PAsp(AED)-CA consisting of poly(ethylene glycol) (PEG), reduction-sensitive poly (N-(2,2'-dithiobis(ethylamine)) aspartamide) PAsp(AED), and cholic acid (CA) was synthesized and assembled into spherical micelles which encapsulated EIA in its hydrophobic core and HRP in a reduction-sensitive interlayer. TEM photographs show that the polymer micelle is around 40 nm, and the cell survival rate test shows that the EIA/HRP polymer micelle is highly lethal to human lung adenocarcinoma cells. Thus, co-delivery of EIA and HRP demonstrates great potential in cancer therapy, offering a structurally simple and highly tunable platform for the synchronous delivery of enzymes and prodrugs in EPT.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Institute of Biochemical Engineering&Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Institute of Biochemical Engineering&Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Institute of Biochemical Engineering&Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Institute of Biochemical Engineering&Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Yuan
authors.affiliation: School of Material Science and Engineering, Lanzhou University of Technology, Lanzhou, 730050, P. R. China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Institute of Biochemical Engineering&Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Institute of Biochemical Engineering&Environmental Technology, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.|Zhongwei High-tech Institute of Lanzhou University, Zhongwei, 755000, P. R. China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D006735:Horseradish Peroxidase / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007210:Indoleacetic Acids / Q000737:chemistry; D007773:Lactates / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D007210:Indoleacetic Acids; D007773:Lactates; D008823:Micelles; D011355:Prodrugs; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; C030737:indoleacetic acid; D006735:Horseradish Peroxidase
keywords: drug delivery; enzymes; horseradish peroxidase; micelles; reactive oxygen species