title: Trigger-responsive, fast-degradable poly(β-amino ester)s for enhanced DNA unpackaging and reduced toxicity.
abstract: Poly(β-amino ester)s (PBAEs) represent an important class of cationic gene delivery materials which, however, suffer from uncontrolled DNA release due in part to the slow degradation of their polyester backbone. Additionally, PBAEs with high molecular weight (MW) also show considerable toxicities. In this study, we designed and developed PBAEs with trigger-responsive domains built-in polymer backbones that can be rapidly cleaved upon external UV light triggering to promote intracellular DNA release as well as reduce material toxicity. Photo-responsive PBAEs were prepared via polyaddition of (2-nitro-1,3-phenylene)bis(methylene) diacrylate and a bifunctional amine. The nitrobenzene moiety was placed in each repeating unit of the PBAE to allow fast response to external UV irradiation, and thus the ester linkers were cleaved and the polymers were degraded within several minutes upon UV irradiation. Cationic PBAEs with high MWs were able to mediate effective intracellular gene delivery, while upon UV irradiation post-transfection, enhanced DNA unpackaging and reduced material toxicity were observed, which collectively contributed to greatly improved transfection efficiencies in various mammalian cell types tested. This strategy allows precise manipulation of material toxicity and gene release profiles of PBAEs, and thus provides an effective design approach to address critical issues in non-viral gene delivery.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA. Electronic address: lcyin@illinois.edu.
authors.forename: Lichen
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA. Electronic address: jianjunc@illinois.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry*; D042003:DNA Packaging; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014162:Transfection
chemical_list: D011091:Polyesters; D011108:Polymers; C507253:poly(beta-amino ester); D004247:DNA
keywords: Cytotoxicity; Degradable polymer; Intracellular DNA release; Non-viral gene delivery; Poly(β-amino ester); Trigger responsiveness