title: Well-defined star polymers for co-delivery of plasmid DNA and imiquimod to dendritic cells.
abstract: Co-delivery of antigen-encoding plasmid DNA (pDNA) and immune-modulatory molecules has importance in advancing gene-based immunotherapy and vaccines. Here novel star polymer nanocarriers were synthesized for co-delivery of pDNA and imiquimod (IMQ), a poorly soluble small-molecule adjuvant, to dendritic cells. Computational modeling and experimental results revealed that the polymers formed either multimolecular or unimolecular core-shell-type micelles in water, depending on the nature of the outer hydrophilic shell. Micelles loaded with both IMQ and pDNA were able to release IMQ in response to intracellular pH of the endo-lysosome and transfect mouse dendritic cells (DC2.4 line) in vitro. Importantly, IMQ-loaded micelle/pDNA complexes displayed much enhanced transfection efficiency than IMQ-free complexes. These results demonstrate the feasibility of co-delivery of pDNA and IMQ to antigen-presenting cells by multifunctional polymer nanocarriers with potential use in gene-based vaccine approaches.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA; School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hanson
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Han
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Yao
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA; College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China.
authors.forename: Hongru
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. Electronic address: celjzh@scut.edu.cn.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Hasselmo Hall, 312 Church Street S.E., Minneapolis, MN 55455, USA. Electronic address: wangx504@umn.edu.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002850:Chromatography, Gel; D004247:DNA / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D018014:Gene Transfer Techniques; D000077271:Imiquimod; D007700:Kinetics; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D014162:Transfection; D014867:Water / Q000737:chemistry
chemical_list: D000634:Aminoquinolines; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D012996:Solutions; D014867:Water; D004247:DNA; D000077271:Imiquimod
keywords: Co-delivery; DNA delivery; Imiquimod; Micelles; Star copolymer