Abstract
We present a cationic polymer architecture composed of phenylboronic acid (PBA), sugar-installed polyethylenimine (PEI), and polyethylene glycol (PEG). The chemical bonding of PBA with the diol in the sugar enabled the crosslinking of low-molecular-weight (MW) PEI to form high-MW PEI, resulting in strong interaction with anionic DNA for gene delivery. Inside the cell, the binding of PBA and sugar was disrupted by either acidic endosomal pH or intracellular ATP, so gene payloads were released effectively. This dual stimuli-responsive gene release drove the polymer to deliver DNA for high transfection efficiency with low cytotoxicity. In addition, PBA moiety with PEGylation facilitated the binding of polymer/DNA polyplexes to sialylated glycoprotein which is overexpressed on the tumor cell membrane, and thus provided high tumor targeting ability. Therapeutic application of our polymer was demonstrated as an anti-angiogenic gene delivery agent for tumor growth inhibition. Our judicious designed polymer structure based on PBA provides enormous potential as a gene delivery agent for effective gene therapy by stimuli-responsiveness and tumor targeting.
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