Polyethylene glycol and polyethylenimine dual-functionalized nano-graphene oxide for photothermally enhanced gene delivery.

Graphene oxide (GO) has been extensively explored in nanomedicine for its excellent physiochemical, electrical, and optical properties. Here, polyethylene glycol (PEG) and polyethylenimine (PEI) are covalently conjugated to GO via amide bonds, obtaining a physiologically stable dual-polymer-functionalized nano-GO conjugate (NGO-PEG-PEI) with ultra-small size. Compared with free PEI and the GO-PEI conjugate without PEGylation, NGO-PEG-PEI shows superior gene transfection efficiency without serum interference, as well as reduced cytotoxicity. Utilizing the NIR optical absorbance of NGO, the cellular uptake of NGO-PEG-PEI is shown to be enhanced under a low power NIR laser irradiation, owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells. As the results, remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO-PEG-PEI as the light-responsive gene carrier. More importantly, it is shown that our NGO-PEG-PEI is able to deliver small interfering RNA (siRNA) into cells under the control of NIR light, resulting in obvious down-regulation of the target gene, Polo-like kinase 1 (Plk1), in the presence of laser irradiation. This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light-controllable gene delivery. This work also encourages further explorations of functionalized nano-GO as a photocontrollable nanovector for combined photothermal and gene therapies.

[1]  Jin-Zhi Du,et al.  Sheddable ternary nanoparticles for tumor acidity-targeted siRNA delivery. , 2012, ACS nano.

[2]  Jin-Zhi Du,et al.  Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. , 2011, Journal of the American Chemical Society.

[3]  D. Wells,et al.  Gene Therapy Progress and Prospects: Electroporation and other physical methods , 2004, Gene Therapy.

[4]  Liangzhu Feng,et al.  Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. , 2011, ACS nano.

[5]  T. Niidome,et al.  Gene Therapy Progress and Prospects: Nonviral vectors , 2002, Gene Therapy.

[6]  Chunhai Fan,et al.  Graphene-based antibacterial paper. , 2010, ACS nano.

[7]  Yang Xu,et al.  Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. , 2010, ACS nano.

[8]  T. Ohtsuki,et al.  Photoinduced RNA interference. , 2012, Accounts of chemical research.

[9]  B. Sproat,et al.  Biophysical characterization of hyper-branched polyethylenimine-graft-polycaprolactone-block-mono-methoxyl-poly(ethylene glycol) copolymers (hy-PEI-PCL-mPEG) for siRNA delivery. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[10]  Leaf Huang,et al.  Gene therapy progress and prospects: non-viral gene therapy by systemic delivery , 2006, Gene Therapy.

[11]  H. Krug,et al.  Oops they did it again! Carbon nanotubes hoax scientists in viability assays. , 2006, Nano letters.

[12]  Kian Ping Loh,et al.  Graphene-based SELDI probe with ultrahigh extraction and sensitivity for DNA oligomer. , 2010, Journal of the American Chemical Society.

[13]  Xiaogang Qu,et al.  Using Graphene Oxide High Near‐Infrared Absorbance for Photothermal Treatment of Alzheimer's Disease , 2012, Advanced materials.

[14]  Lin Ji,et al.  Gene silencing by gold nanoshell-mediated delivery and laser-triggered release of antisense oligonucleotide and siRNA. , 2012, ACS nano.

[15]  Yi-Cheng Chen,et al.  DNA-gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. , 2006, Journal of the American Chemical Society.

[16]  Kai Yang,et al.  The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. , 2012, Biomaterials.

[17]  Deepthy Menon,et al.  Hemocompatibility and macrophage response of pristine and functionalized graphene. , 2012, Small.

[18]  Liangzhu Feng,et al.  Graphene in biomedicine: opportunities and challenges. , 2011, Nanomedicine.

[19]  Zhuang Liu,et al.  PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. , 2008, Journal of the American Chemical Society.

[20]  Zhijun Zhang,et al.  Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. , 2010, Small.

[21]  B. Beckmann,et al.  Polymer-related off-target effects in non-viral siRNA delivery. , 2011, Biomaterials.

[22]  Kai Yang,et al.  Multimodal Imaging Guided Photothermal Therapy using Functionalized Graphene Nanosheets Anchored with Magnetic Nanoparticles , 2012, Advanced materials.

[23]  Daniel G. Anderson,et al.  Knocking down barriers: advances in siRNA delivery , 2009, Nature Reviews Drug Discovery.

[24]  J. A. George,et al.  Gene therapy progress and prospects: adenoviral vectors , 2003, Gene Therapy.

[25]  Zhouyi Guo,et al.  Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. , 2011, Biomaterials.

[26]  Ronnie H. Fang,et al.  In vivo clearance and toxicity of monodisperse iron oxide nanocrystals. , 2012, ACS nano.

[27]  H. Dai,et al.  Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. , 2011, Journal of the American Chemical Society.

[28]  Matthew Tirrell,et al.  Laser-Activated Gene Silencing via Gold Nanoshell-siRNA Conjugates. , 2009, ACS nano.

[29]  Hua Zhang,et al.  Graphene-based composites. , 2012, Chemical Society reviews.

[30]  Jiali Zhang,et al.  Biocompatibility of Graphene Oxide , 2010, Nanoscale research letters.

[31]  Hongjie Dai,et al.  Multifunctional FeCo-graphitic carbon nanocrystals for combined imaging, drug delivery and tumor-specific photothermal therapy in mice , 2011 .

[32]  Zhuang Liu,et al.  Nano-graphene oxide for cellular imaging and drug delivery , 2008, Nano research.

[33]  Kai Yang,et al.  Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. , 2010, Nano letters.

[34]  H. Dai,et al.  Photothermally enhanced drug delivery by ultrasmall multifunctional FeCo/graphitic shell nanocrystals. , 2011, ACS nano.

[35]  Kai Yang,et al.  Organic stealth nanoparticles for highly effective in vivo near-infrared photothermal therapy of cancer. , 2012, ACS nano.

[36]  Kai Yang,et al.  In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. , 2011, ACS nano.

[37]  C. Fan,et al.  Protein corona-mediated mitigation of cytotoxicity of graphene oxide. , 2011, ACS nano.

[38]  Deepthy Menon,et al.  Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. , 2011, Nanoscale.

[39]  Zhuang Liu,et al.  Graphene based gene transfection. , 2011, Nanoscale.

[40]  E. Wagner,et al.  Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. , 2008, Bioconjugate chemistry.

[41]  Yong Zhang,et al.  Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers , 2012, Proceedings of the National Academy of Sciences.

[42]  Zhuoxuan Lu,et al.  Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide. , 2011, Small.