Photoluminescent graphene nanoparticles for cancer phototherapy and imaging.

Graphene-based nanomaterials are of great interest in a wide range of applications in electronics, the environment, and energy as well as in biomedical and bioengineering. Their unique properties make them generally applicable as prognostic, diagnostic, and therapeutic agents in cancer. In this work, we focused on photodynamic and photothermal therapeutic properties of our previously synthesized carboxylated photoluminescent graphene nanodots (cGdots). The cGdots are ∼5 nm in diameter and excited at 655 nm. Our findings reveal that, upon laser irradiation by near-infrared (wavelength 670 nm) sensitizer, electrons of the cGdots starts to vibrate and form electron clouds, thereby generating sufficient heat (>50 °C) to kill the cancer cells by thermal ablation. The generation of singlet oxygen also occurs due to irradiation, thus acting similarly to pheophorbide-A, a well-known photodynamic therapeutic agent. The cGdots kills MDA-MB231 cancer cells (more than 70%) through both photodynamic and photothermal effects. The cGdots were equally effective in the in vivo model of MDA-MB231 xenografted tumor-bearing mice also as observed for 21 days. The cGdot was intravenously injected, and the tumor was irradiated by laser, resulting in final volume of tumor was ∼70% smaller than that of saline-treated tumor. It indicates that the growth rate of cGdot-treated tumor was slower compared to saline-treated tumor. The synthesized cGdots could enable visualization of tumor tissue in mice, thereby illustrating their use as optical imaging agents for detecting cancer noninvasively in deep tissue/organ. Collectively, our findings reveal that multimodal cGdots can be used for phototherapy, through photothermal or photodynamic effects, and for noninvasive optical imaging of deep tissues and tumors simultaneously.

[1]  W. Choi,et al.  Emissive ZnO-graphene quantum dots for white-light-emitting diodes. , 2012, Nature nanotechnology.

[2]  L. Qu,et al.  Graphene-quantum-dot assembled nanotubes: a new platform for efficient Raman enhancement. , 2012, ACS nano.

[3]  Dwight G Nishimura,et al.  FeCo/graphitic-shell nanocrystals as advanced magnetic-resonance-imaging and near-infrared agents , 2006, Nature materials.

[4]  Rui Hu,et al.  A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. , 2012, Nature nanotechnology.

[5]  M. Nurunnabi,et al.  A photosensitizer-conjugated magnetic iron oxide/gold hybrid nanoparticle as an activatable platform for photodynamic cancer therapy. , 2014, Journal of materials chemistry. B.

[6]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[7]  Shuguang Zhang,et al.  Nanotechnology: Peptides as biological semiconductors , 2010, Nature.

[8]  M. Nurunnabi,et al.  Surface coating of graphene quantum dots using mussel-inspired polydopamine for biomedical optical imaging. , 2013, ACS applied materials & interfaces.

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

[10]  Jin-Oh You,et al.  A drug-delivery vehicle combining the targeting and thermal ablation of HER2+ breast-cancer cells with triggered drug release. , 2013, Angewandte Chemie.

[11]  Xin Yan,et al.  Synthesis of large, stable colloidal graphene quantum dots with tunable size. , 2010, Journal of the American Chemical Society.

[12]  Peter Gölitz,et al.  Cover Picture: Champagne and Fireworks: Angewandte Chemie Celebrates Its Birthday (Angew. Chem. Int. Ed. 1/2013) , 2013 .

[13]  Andrés J. García,et al.  Human stem cell delivery for treatment of large segmental bone defects , 2010, Proceedings of the National Academy of Sciences.

[14]  Younan Xia,et al.  Nanomedicine: swarming towards the target. , 2011, Nature materials.

[15]  B. K. Gupta,et al.  Graphene quantum dots derived from carbon fibers. , 2012, Nano letters.

[16]  Dong Yun Lee,et al.  In vivo biodistribution and toxicology of carboxylated graphene quantum dots. , 2013, ACS nano.

[17]  D. A. Russell,et al.  Targeting the oncofetal Thomsen-Friedenreich disaccharide using jacalin-PEG phthalocyanine gold nanoparticles for photodynamic cancer therapy. , 2012, Angewandte Chemie.

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

[19]  R. Weissleder,et al.  Imaging in the era of molecular oncology , 2008, Nature.

[20]  Zahi A. Fayad,et al.  Imaging of atherosclerotic cardiovascular disease , 2008, Nature.

[21]  S. Nie,et al.  Quantum dot bioconjugates for ultrasensitive nonisotopic detection. , 1998, Science.

[22]  C. D. Geddes,et al.  Plasmonic engineering of singlet oxygen generation , 2008, Proceedings of the National Academy of Sciences.

[23]  R. Allman,et al.  Effect of photodynamic therapy in combination with mitomycin C on a mitomycin-resistant bladder cancer cell line. , 1997, British Journal of Cancer.

[24]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[25]  Hua Su,et al.  Multifunctional quantum-dot-based siRNA delivery for HPV18 E6 gene silence and intracellular imaging. , 2011, Biomaterials.

[26]  Jacob M. Taylor,et al.  Coherent Manipulation of Coupled Electron Spins in Semiconductor Quantum Dots , 2005, Science.

[27]  Kang Moo Huh,et al.  Targeted near-IR QDs-loaded micelles for cancer therapy and imaging. , 2010, Biomaterials.

[28]  Amir Yacoby,et al.  Dephasing time of GaAs electron-spin qubits coupled to a nuclear bath exceeding 200 μs , 2011 .

[29]  Dong Yun Lee,et al.  Near infra-red photoluminescent graphene nanoparticles greatly expand their use in noninvasive biomedical imaging. , 2013, Chemical communications.

[30]  A. Ferrari,et al.  Graphene Photonics and Optoelectroncs , 2010, CLEO 2012.

[31]  Adele E. Schmitz,et al.  Coherent singlet-triplet oscillations in a silicon-based double quantum dot , 2012, Nature.

[32]  Jingyan Zhang,et al.  Stabilization and induction of oligonucleotide i-motif structure via graphene quantum dots. , 2013, ACS nano.

[33]  Nurunnabi,et al.  GSH-mediated photoactivity of pheophorbide a-conjugated heparin/gold nanoparticle for photodynamic therapy. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Nurunnabi,et al.  Oral absorption mechanism and anti-angiogenesis effect of taurocholic acid-linked heparin-docetaxel conjugates. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Nicholas A Peppas,et al.  Theranostic agents for intracellular gene delivery with spatiotemporal imaging. , 2013, Nano today.

[36]  Yu Liu,et al.  Structural and electronic properties of T graphene: a two-dimensional carbon allotrope with tetrarings. , 2013, Physical review letters.