title: Cell penetrating peptide-based polyplexes shelled with polysaccharide to improve stability and gene transfection.
abstract: Cell-penetrating peptides (CPP) have been widely developed as a strategy to enhance cell penetrating ability and transfection. In this work, octa-arginine modified dextran gene vector with pH-sensitivity was developed via host-guest interactions. α-Cyclodextrin was modified with octa-arginine (CDR), which had excellent cell penetrating ability. Dextran was selected as a backbone and modified with azobenzene as guest units by acid-labile imine bonds (Az-I-Dex). The supramolecular polymer CDR/Az-I-Dex with high a C/A molar ratio (molar ratio of CD on CDR to Az on Az-I-Dex) was unfavorable for DNA condensation. The dextran shell of CDR/Az-I-Dex/DNA polyplexes improved the stability under physiological conditions. However, once treated with acetate buffer (pH 5.4) for 3 h, large aggregates formed rapidly due to the cleavage of the dextran shell. As expected, the vector had cell viability of 80% even when the CDR concentration increased to 100 μg mL(-1). Moreover, due to the effective cellular uptake efficiency, CDR/Az-I-Dex/DNA polyplexes had 6-300 times higher transfection efficiency than CDR/DNA polyplexes. It was even higher than high molecular weight PLL-based polyplexes of HEK293 T cells. Importantly, chloroquine as an endosomal escape agent could not improve the transfection of CDR/Az-I-Dex/DNA polyplexes, which indicated that the CDR/Az-I-Dex supramolecular polymer had its own ability for endosomal escape. These results suggested that the CPP-based polyplexes shelled with polysaccharide can be promising non-viral gene delivery carriers.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. China. yx_wang@zju.edu.cn.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Li
authors.forename: Yajie
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianwei
authors.initials: J
authors.lastname: Du
authors.forename: Kefeng
authors.initials: K
authors.lastname: Ren
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D019556:COS Cells; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D002522:Chlorocebus aethiops; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D003911:Dextrans / Q000737:chemistry; D004058:Diffusion; D004355:Drug Stability; D057809:HEK293 Cells; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D011134:Polysaccharides / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D057846:Cell-Penetrating Peptides; D020099:Coated Materials, Biocompatible; D003911:Dextrans; D053769:Nanocapsules; D011134:Polysaccharides; D004247:DNA