title: Main-chain degradable single-chain cyclized polymers as gene delivery vectors.
abstract: Single-chain technology (SCT) allows the manipulation of polymeric architectures at an individual polymer chain level, providing a new platform for the fabrication of nanoscale polymeric objects. However, it remains problematic to apply this newborn technology to the biological and medical fields, since synthesis of single-chain polymeric nanoparticles relies heavily on controlled/living radical polymerization of vinyl based monomers, yielding a persistent non-degradable carbon-carbon based backbone. Moreover, the ultrahigh dilution conditions often required for single-chain polymer nanoparticle synthesis limits large-scale applicability. A versatile approach to achieve backbone degradability in single-chain cyclized polymers was developed by combining ring-opening addition polymerization and intramolecular cyclization into a one-pot RAFT copolymerization of cyclic and mono/multi-vinyl monomers system under concentrated conditions. The in situ intramolecular cyclization of individual propagating chains was achieved by kinetic control and statistical manipulation of mono- and multi-vinyl monomer copolymerization. The cyclic allylsulfide monomer 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MDTD) was copolymerized via the ring-opening pathway to introduce disulfide groups into the vinyl-based backbone without compromising the single chain propagation nature. Backbone degradable single chain polymeric nanoparticles were obtained with molecular weights of 10kDa and MDTD incorporation ratios of 4.7%. Chemical degradation of the nanoparticles confirmed both their single chain nature, as well as backbone degradability. The single-chain cyclized polymeric nanoparticles were evaluated for their gene transfection capabilities. The backbone degradable nanoparticles displayed high transfection efficiencies and low cytotoxicities in both 3T3 and HeLa cells.
authors.affiliation: Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Department of Biomaterials Science and Technology, University of Twente, Drienerlolaan 5, Enschede, The Netherlands.
authors.forename: Verena I
authors.initials: VI
authors.lastname: Böhmer
authors.affiliation: Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Dezhong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: wenxin.wang@ucd.ie.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biomaterials Science and Technology, University of Twente, Drienerlolaan 5, Enschede, The Netherlands; Department of Nuclear Medicine and Molecular Imaging University, Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands. Electronic address: j.m.j.paulusse@utwente.nl.
authors.forename: Jos M J
authors.initials: JM
authors.lastname: Paulusse
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D011108:Polymers; D049452:Green Fluorescent Proteins; D004247:DNA
keywords: Degradability; Gene delivery; Polymer nanoparticles; Radical ring opening polymerization; Single chain technology