title: Poly-L-Lysine-Poly[HPMA] Block Copolymers Obtained by RAFT Polymerization as Polyplex-Transfection Reagents with Minimal Toxicity.
abstract: Herein we describe the synthesis of poly-L-lysine-b-poly[N-(2-hydroxypropyl)-metha-crylamide)] (poly[HPMA]) block copolymers by combination of solid phase peptide synthesis or polymerization of α-amino acid-N-carboxy-anhydrides (NCA-polymerization) with the reversible addition-fragmentation chain transfer polymerization (RAFT). In the presence of p-DNA, these polymers form polyplex micelles with a size of 100-200 nm in diameter (monitored by SDS-PAGE and FCS). Primary in vitro studies with HEK-293T cells reveal their cellular uptake (FACS studies and CLSM) and proof successful transfection with efficiencies depending on the length of polylysine. Moreover, these polyplexes display minimal toxicity (MTT-assay and FACS-measurements) featuring a p[HPMA] corona for efficient extracellular shielding and the potential ligation with antibodies.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Kristof
authors.initials: K
authors.lastname: Tappertzhofen
authors.affiliation: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Weiser
authors.affiliation: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Montermann
authors.affiliation: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Reske-Kunz
authors.affiliation: Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany. mbros@uni-mainz.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. zentel@uni-mainz.de.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zentel
mesh_terms: D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008689:Methacrylates / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D011107:Polylysine / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D058105:Polymerization; D014162:Transfection
chemical_list: D008689:Methacrylates; D011107:Polylysine; D004247:DNA; C032802:hydroxypropyl methacrylate
keywords: RAFT polymerization; block copolymers; polyplexes; transfection