title: Stimuli-Regulated Enzymatically Degradable Smart Graphene-Oxide-Polymer Nanocarrier Facilitating Photothermal Gene Delivery.
abstract: Graphene oxide (GO) has attracted huge interest in the area of biomedical application due to its unique physicochemical properties, but the issue of long-term toxicity in the body remains unclear. Here, the rationally designed GO nanocarriers (ssPEG-PEI-GO) modified with polyethylene glycol (PEG) and branched polyethylenimine (BPEI) via disulfide linkage are described to control the biological activity of GO as a delivery carrier and its degradation in biological systems. The ssPEG-PEI-GO efficiently interacts with plasmid DNA (pDNA) to form a stable nanocomplex by electrostatic interaction. After cellular uptake, ssPEG-PEI-GO/pDNA complex can easily escape from endosomes by photothermal conversion of GO upon near-infrared irradiation and subsequent photothermally induced endosome disruption. After endosomal escape, reducing intracellular environment enables polymer dissociation and rapid gene release and therefore shows enhanced gene transfection efficiency with low toxicity in comparison with non-reducible amide-functionalized GO nanocarriers (amPEG-PEI-GO) and control BPEIs. Besides, dePEGylated GO nanocarrier, owing to its disulfide bond, exhibits higher entrapment by macrophages compared with amide-functionalized one and subsequently degrades in macrophage. The degradation process can be monitored by photoluminescence emitted from degraded GO. These results suggest new directions in the design of biodegradable and multifunctional GO-based nanocarrier for biomedical application.
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), 77 Cheongam-Ro, Nam-GuPohang, 37673, Republic of Korea.|Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), 77 Cheongam-Ro, Nam-GuPohang, 37673, Republic of Korea.|Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center for Artificial Low Dimensional Electronic System, Institute for Basic Science (IBS), 77 Cheongam-Ro, Nam-Gu, Pohang, 37673, Republic of Korea.|Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Center for Artificial Low Dimensional Electronic System, Institute for Basic Science (IBS), 77 Cheongam-Ro, Nam-Gu, Pohang, 37673, Republic of Korea.|Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
authors.forename: Hee Cheul
authors.initials: HC
authors.lastname: Choi
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science (IBS), 77 Cheongam-Ro, Nam-GuPohang, 37673, Republic of Korea.|Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006108:Graphite / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011094:Polyethyleneimine / Q000493:pharmacokinetics / Q000494:pharmacology; D000067996:RAW 264.7 Cells
chemical_list: D011092:Polyethylene Glycols; D006108:Graphite; D011094:Polyethyleneimine; D004247:DNA; C000595213:polyethylene glycol 400
keywords: biodegradation; bioreducible; gene delivery; graphene oxide-polymer composite; photothermal