Photothermally triggered cytosolic drug delivery via endosome disruption using a functionalized reduced graphene oxide.

Graphene oxide has unique physiochemical properties, showing great potential in biomedical applications. In the present work, functionalized reduced graphene oxide (PEG-BPEI-rGO) has been developed as a nanotemplate for photothermally triggered cytosolic drug delivery by inducing endosomal disruption and subsequent drug release. PEG-BPEI-rGO has the ability to load a greater amount of doxorubicin (DOX) than unreduced PEG-BPEI-GO via π-π and hydrophobic interactions, showing high water stability. Loaded DOX could be efficiently released by glutathione (GSH) and the photothermal effect of irradiated near IR (NIR) in test tubes as well as in cells. Importantly, PEG-BPEI-rGO/DOX complex was found to escape from endosomes after cellular uptake by photothermally induced endosomal disruption and the proton sponge effect, followed by GSH-induced DOX release into the cytosol. Finally, it was concluded that a greater cancer cell death efficacy was observed in PEG-BPEI-rGO/DOX complex-treated cells with NIR irradiation than those with no irradiation. This study demonstrated the development of the potential of a PEG-BPEI-rGO nanocarrier by photothermally triggered cytosolic drug delivery via endosomal disruption.

[1]  S. D. De Smedt,et al.  Ultrasound responsive doxorubicin-loaded microbubbles; towards an easy applicable drug delivery platform. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[2]  S. Matsuo,et al.  Mechanism of specific nuclear transport of adriamycin: the mode of nuclear translocation of adriamycin-proteasome complex. , 2001, Cancer research.

[3]  Brian P. Timko,et al.  Remotely Triggerable Drug Delivery Systems , 2010, Advanced materials.

[4]  Kevin Braeckmans,et al.  Light-addressable capsules as caged compound matrix for controlled triggering of cytosolic reactions. , 2013, Angewandte Chemie.

[5]  Jin-Oh You,et al.  The effect of swelling and cationic character on gene transfection by pH-sensitive nanocarriers. , 2010, Biomaterials.

[6]  Il-Kwon Oh,et al.  Graphene oxide-polyethylenimine nanoconstruct as a gene delivery vector and bioimaging tool. , 2011, Bioconjugate chemistry.

[7]  Visualizing graphene based sheets by fluorescence quenching microscopy. , 2009, Journal of the American Chemical Society.

[8]  Zhenpeng Qin,et al.  Thermophysical and biological responses of gold nanoparticle laser heating. , 2012, Chemical Society reviews.

[9]  H. Choi,et al.  In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. , 2009, ACS Nano.

[10]  Robert Langer,et al.  A magnetically triggered composite membrane for on-demand drug delivery. , 2009, Nano letters.

[11]  Wenlin Huang,et al.  Targeted minicircle DNA delivery using folate-poly(ethylene glycol)-polyethylenimine as non-viral carrier. , 2010, Biomaterials.

[12]  R. Weissleder.  A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

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

[14]  Xin Cai,et al.  A new theranostic system based on gold nanocages and phase-change materials with unique features for photoacoustic imaging and controlled release. , 2011, Journal of the American Chemical Society.

[15]  Wah Chiu,et al.  Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells. , 2008, Journal of the American Chemical Society.

[16]  Fong-Yu Cheng,et al.  Near‐Infrared Light‐Responsive Intracellular Drug and siRNA Release Using Au Nanoensembles with Oligonucleotide‐Capped Silica Shell , 2012, Advanced materials.

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

[18]  Won Jong Kim,et al.  Photothermally controlled gene delivery by reduced graphene oxide-polyethylenimine nanocomposite. , 2014, Small.

[19]  Hongjie Dai,et al.  Supramolecular Chemistry on Water- Soluble Carbon Nanotubes for Drug Loading and Delivery , 2007 .

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

[21]  V. Maheshwari,et al.  Adsorption and desorption of DNA on graphene oxide studied by fluorescently labeled oligonucleotides. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[22]  Chulhee Kim,et al.  Photoinduced release of guest molecules by supramolecular transformation of self-assembled aggregates derived from dendrons. , 2008, Angewandte Chemie.

[23]  Emanuel Fleige,et al.  Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: concepts and applications. , 2012, Advanced drug delivery reviews.

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

[25]  Chen-Yuan Dong,et al.  Multiple release kinetics of targeted drug from gold nanorod embedded polyelectrolyte conjugates induced by near-infrared laser irradiation. , 2010, Journal of the American Chemical Society.

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

[27]  R. Ruoff,et al.  Reduced graphene oxide by chemical graphitization. , 2010, Nature communications.

[28]  Mira Kim,et al.  A spatiotemporal anticancer drug release platform of PEGylated graphene oxide triggered by glutathione in vitro and in vivo , 2012 .

[29]  Younan Xia,et al.  Gold nanocages covered by smart polymers for controlled release with near-infrared light , 2009, Nature materials.

[30]  Won Jong Kim,et al.  Bioreducible polymers for gene silencing and delivery. , 2012, Accounts of chemical research.

[31]  Yuan Ping,et al.  Chitosan-functionalized graphene oxide as a nanocarrier for drug and gene delivery. , 2011, Small.

[32]  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.

[33]  S. Thayumanavan,et al.  Temperature-sensitive dendritic micelles. , 2005, Journal of the American Chemical Society.

[34]  Imre Dékány,et al.  Evolution of surface functional groups in a series of progressively oxidized graphite oxides , 2006 .

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

[36]  H. Olin,et al.  Carbon nanomaterials as drug carriers: Real time drug release investigation , 2012 .

[37]  V. Sée,et al.  Inflicting controlled nonthermal damage to subcellular structures by laser-activated gold nanoparticles. , 2010, Nano letters.

[38]  I-Wei Chen,et al.  Quantum‐Dot‐Tagged Reduced Graphene Oxide Nanocomposites for Bright Fluorescence Bioimaging and Photothermal Therapy Monitored In Situ , 2012, Advanced materials.

[39]  Alexander L. Klibanov,et al.  Microbubbles in ultrasound-triggered drug and gene delivery. , 2008, Advanced drug delivery reviews.

[40]  Wolfgang J Parak,et al.  NIR-light triggered delivery of macromolecules into the cytosol. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

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

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

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

[44]  Abhishek Sahu,et al.  A stimuli-sensitive injectable graphene oxide composite hydrogel. , 2012, Chemical communications.

[45]  Omid Akhavan,et al.  The use of a glucose-reduced graphene oxide suspension for photothermal cancer therapy , 2012 .