title: Self-assembled vehicle construction via boronic acid coupling and host-guest interaction for serum-tolerant DNA transport and pH-responsive drug delivery.
abstract: By exploiting boronic acid coupling and host-guest chemistry, a pH-responsive drug/gene co-delivery nanoplatform is designed for cancer treatments with the excellently serum-tolerant transfection activity and the capability to load and release hydrophobic drugs in an acidity-accelerated manner. Via boronate linkage, γ-CD is allowed to spontaneously attach onto phenylboronic-acid-modified oligoethylenimine (PEI1.8K-PB2.9 ) at neutral condition. The formed vehicle/DNA nanoformulation is thus surrounded densely by γ-CD moieties to biomimic the carbohydrate-rich cell surface, providing a novel approach to overcome serum-susceptible drawbacks frequently associated with synthetic gene carriers. PEI1.8K-PB2.9 -γ-CD conjugates demonstrate significantly improved cell-biocompatibility and transfection activity over PEI1.8K-PB2.9 . Noticeably, serum-associated inhibition effect is negligible for PEI1.8K-PB2.9 -γ-CD-mediated transfection whereas marked transfection reduction occurs for PEI25K and PEI1.8K-PB2.9 upon serum exposure. Consequently, PEI1.8K-PB2.9 -γ-CDs afford much higher transfection efficiency, that is, 25-fold higher luciferase expression over PEI25K in presence of 30% serum. An anticancer drug of doxorubicin (DOX) is shown to be readily accommodated into the nanoformulation via host-guest chemistry and intracellularly co-delivered together with plasmid DNA. Due to the acidity-labile feature of boronate linkage, DOX/γ-CD inclusion complexes would be mostly detached from the nanoformulation triggered by acidity, leading to faster drug release. Furthermore, drug inclusion does not alter the serum-compatible transfection efficiency of PEI1.8K-PB2.9 -γ-CD.
authors: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors: Bin
authors: B
authors: Yang
authors: Huizhen
authors: H
authors: Jia
authors: Xuli
authors: X
authors: Wang
authors: Si
authors: S
authors: Chen
authors: Xianzheng
authors: X
authors: Zhang
authors: Renxi
authors: R
authors: Zhuo
authors: Jun
authors: J
authors: Feng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047408:gamma-Cyclodextrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D001897:Boronic Acids; D004337:Drug Carriers; D047408:gamma-Cyclodextrins; D004317:Doxorubicin; C010686:benzeneboronic acid
keywords: drug inclusion; gene delivery; pH-responsive drug release; serum-tolerability