Selective Uptake of Cylindrical Poly(2-Oxazoline) Brush-AntiDEC205 Antibody-OVA Antigen Conjugates into DEC-Positive Dendritic Cells and Subsequent T-Cell Activation

被引:40
作者
Buehler, Jasmin [1 ,2 ]
Gietzen, Sabine [1 ]
Reuter, Anika [1 ,3 ]
Kappel, Cinja [5 ]
Fischer, Karl [1 ]
Decker, Sandra [1 ]
Schaefel, David [4 ]
Koynov, Kaloian [4 ]
Bros, Matthias [5 ]
Tubbe, Ingrid [5 ]
Grabbe, Stephan [3 ,5 ]
Schmidt, Manfred [1 ,2 ,3 ]
机构
[1] Johannes Gutenberg Univ Mainz, Inst Phys Chem, D-55099 Mainz, Germany
[2] Grad Sch Mat Sci, D-55128 Mainz, Germany
[3] Max Planck Grad Ctr, D-55128 Mainz, Germany
[4] Max Planck Inst Polymer Res, D-55128 Mainz, Germany
[5] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Dermatol, D-55131 Mainz, Germany
关键词
brush polymers; cancer therapy; dendritic cells; nanocarriers; T-cells; GRAFT-COPOLYMERS; HPMA COPOLYMERS; STEADY-STATE; POLYMER; BIODISTRIBUTION; CYTOTOXICITY; INHIBITION; BRUSHES; RELEASE; ORIGINS;
D O I
10.1002/chem.201403942
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2-oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205(+)-positive mouse bone marrow-derived dendritic cells (BMDC) was observed, whereas binding and uptake by DEC205(-) negative BMDC and non-DC was essentially absent. Additional conjugation of an antigen peptide yielded a multifunctional polymer structure with a much stronger antigen-specific T-cell stimulatory capacity of pretreated BMDC than application of antigen or polymer-antigen conjugate.
引用
收藏
页码:12405 / 12410
页数:6
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