Phenylboronic acid-sugar grafted polymer architecture as a dual stimuli-responsive gene carrier for targeted anti-angiogenic tumor therapy.
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.
Department of Chemistry, Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea.
Jinhwan
J
Kim
Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.
Yeong Mi
YM
Lee
Department of Chemistry, Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea.
Hyunwoo
H
Kim
Department of Chemistry, Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea.
Dongsik
D
Park
Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea.
Jihoon
J
Kim
Department of Chemistry, Polymer Research Institute, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea; Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 790-784, Republic of Korea. Electronic address: wjkim@postech.ac.kr.
Won Jong
WJ
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001897:Boronic Acids / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005822:Genetic Vectors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects; D014162:Transfection
D000970:Antineoplastic Agents; D001897:Boronic Acids; D002241:Carbohydrates; D011108:Polymers; D011092:Polyethylene Glycols; D004247:DNA; C010686:benzeneboronic acid
Anti-angiogenesis; Gene delivery; Intracellular stimuli; Phenylboronic acid; Tumor targeting