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Self‐Assembled Vehicle Construction via Boronic Acid Coupling and Host–Guest Interaction for Serum‐Tolerant DNA Transport and pH‐Responsive Drug Delivery
Author(s) -
Yang Bin,
Jia Huizhen,
Wang Xuli,
Chen Si,
Zhang Xianzheng,
Zhuo Renxi,
Feng Jun
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300162
Subject(s) - transfection , chemistry , boronic acid , phenylboronic acid , biocompatibility , dna , gene delivery , drug delivery , combinatorial chemistry , biophysics , biochemistry , gene , organic chemistry , biology , catalysis
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‐PB 2.9 ) 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‐PB 2.9 ‐ γ ‐CD conjugates demonstrate significantly improved cell‐biocompatibility and transfection activity over PEI1.8K‐PB 2.9 . Noticeably, serum‐associated inhibition effect is negligible for PEI1.8K‐PB 2.9 ‐ γ ‐CD‐mediated transfection whereas marked transfection reduction occurs for PEI25K and PEI1.8K‐PB 2.9 upon serum exposure. Consequently, PEI1.8K‐PB 2.9 ‐ 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‐PB 2.9 ‐ γ ‐CD.