title: Polymeric assembly of hyperbranched building blocks to establish tunable nanoplatforms for lysosome acidity-responsive gene/drug co-delivery.
abstract: This study plans to develop a nanoparticle technology that can assemble different polymeric "building blocks" with various desired functionalities into one nanosystem in a pH-dependent manner. For this purpose, polymeric building blocks were specifically designed with hyperbranched architectures, and orthogonal pH-reversible phenylboronic acid-diols were taken as "joints" to integrate them together. To verify the idea, a corona-core dual-polymer nanoassembly was prepared as the vehicle for lysosomotropic gene/drug co-delivery. Phenylboronic acid modified hyperbranched oligoethylenimine (OEI-PBA) was arranged to cluster around the hydrophobic core composed of hyperbranched polyglycerol, just by mixing two polymers in an appropriate ratio at neutral conditions. Compared with the parent OEI-PBA, this nanoassembly demonstrated better capture of plasmid DNA, highly enhanced activity for cellular transport and gene transfection (up to 100 fold), the ability to further load hydrophobic drugs, lysosome acidity-targeting pH-dependent release of both carried cargoes, and improved cell-biocompatibility. To evaluate its potential for combinational gene/drug therapy, in vitro experiments using the therapeutic p53 gene and antitumor doxorubicin as models were carried out. This intracellular co-delivery led to apparently synergetic anti-cancer effects in cultured cancer cells. This dynamic paradigm shows interesting features including easy manipulation, reversible conjugation, lysosome-targeting pH-responsiveness, high co-delivery efficiency, and functional expandability by further accommodating other building blocks.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, China. fengjun@whu.edu.cn.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Jia
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Wei-Hai
authors.initials: WH
authors.lastname: Chen
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Zhao
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D005990:Glycerol / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008247:Lysosomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009369:Neoplasms / Q000628:therapy*; D011108:Polymers / Q000737:chemistry*
chemical_list: D001897:Boronic Acids; D011108:Polymers; C043941:polyglycerol; D004317:Doxorubicin; C010686:benzeneboronic acid; D005990:Glycerol