Multifunctional graphene quantum dots for combined photothermal and photodynamic therapy coupled with cancer cell tracking applications

Graphene quantum dots (GQDs) have gained enormous attention due to their unique optical properties and emerging employment in biology. Herein, we report the synthesis of highly crystalline GQDs having superior physicochemical and near infrared (NIR)-responsive properties using simple waste, withered leaves of Ficus racemosa, an Indian fig tree, as a carbon source. A considerably large production yield was obtained (ca. 18%) with a competitive quantum yield of 14.16%. The GQDs exhibited excellent dispersibility in both organic as well as aqueous solvents and were highly photostable. High-resolution transmission electron microscopy showed the presence of ultra-small honey-combed as well as self-assembled GQDs. Cell cycle analysis using flow cytometry and biocompatibility studies showed that the GQDs were cytocompatible and were used as in situ labeling probes for normal as well as cancer cells. Furthermore, upon irradiation with an 808 nm laser (0.5 W cm−2), a concentration-dependent photothermal response and production of reactive oxygen species were observed. Confocal laser scanning microscopy showed that GQDs did not lose their fluorescence despite continuous laser irradiation (30 min) on MDA-MB-231 breast cancer cells. Thus, cell death could be traced using GQD-labeled MDA-MB-231 cells post-therapy using the photostability of GQDs, unlike photo-bleachable organic dyes. Thus, a low-cost, scalable, green-synthesis of GQDs with highly efficient optical properties will pave the way for new therapeutics and imaging in biomedical cancer research.

[1]  R. Srivastava,et al.  Graphene Quantum Dots from Mangifera indica: Application in Near-Infrared Bioimaging and Intracellular Nanothermometry , 2017 .

[2]  Maheshwar Sharon,et al.  Milk-derived multi-fluorescent graphene quantum dot-based cancer theranostic system. , 2016, Materials science & engineering. C, Materials for biological applications.

[3]  R. Srivastava,et al.  Albumin stabilized gold nanostars: a biocompatible nanoplatform for SERS, CT imaging and photothermal therapy of cancer , 2016 .

[4]  Dinesh Kumar,et al.  Isolated flavonoids from Ficus racemosa stem bark possess antidiabetic, hypolipidemic and protective effects in albino Wistar rats. , 2016, Journal of ethnopharmacology.

[5]  Josef Skopalik,et al.  Toxicity of carbon dots – Effect of surface functionalization on the cell viability, reactive oxygen species generation and cell cycle , 2016 .

[6]  H. Xiong,et al.  Full-Color Light-Emitting Carbon Dots with a Surface-State-Controlled Luminescence Mechanism. , 2015, ACS nano.

[7]  V. Pavlović,et al.  Modification of Structural and Luminescence Properties of Graphene Quantum Dots by Gamma Irradiation and Their Application in a Photodynamic Therapy. , 2015, ACS applied materials & interfaces.

[8]  O. Wolfbeis.  An overview of nanoparticles commonly used in fluorescent bioimaging. , 2015, Chemical Society reviews.

[9]  Mira Park,et al.  Synthesis of carbon quantum dots from cabbage with down- and up-conversion photoluminescence properties: excellent imaging agent for biomedical applications , 2015 .

[10]  Shiguo Sun,et al.  Recent applications of carbon nanomaterials in fluorescence biosensing and bioimaging. , 2015, Chemical communications.

[11]  Roopa Dharmatti,et al.  Biogenic Synthesis of Fluorescent Carbon Dots at Ambient Temperature Using Azadirachta indica (Neem) gum , 2015, Journal of Fluorescence.

[12]  Jianfeng Chen,et al.  Can graphene quantum dots cause DNA damage in cells? , 2015, Nanoscale.

[13]  I. Matai,et al.  Self-Assembled Hybrids of Fluorescent Carbon Dots and PAMAM Dendrimers for Epirubicin Delivery and Intracellular Imaging. , 2015, ACS applied materials & interfaces.

[14]  Hui-Fen Wu,et al.  Synthesis of highly fluorescent hydrophobic carbon dots by hot injection method using Paraplast as precursor. , 2015, Materials science & engineering. C, Materials for biological applications.

[15]  D. Pang,et al.  Photoluminescence‐Tunable Carbon Nanodots: Surface‐State Energy‐Gap Tuning , 2015, Advanced materials.

[16]  Yuguo Tang,et al.  Recent advances in carbon nanodots: synthesis, properties and biomedical applications. , 2015, Nanoscale.

[17]  Renu Malhotra,et al.  In vivo analysis of biodegradable liposome gold nanoparticles as efficient agents for photothermal therapy of cancer. , 2015, Nano letters.

[18]  W. Duan,et al.  Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages. , 2015, Toxicology.

[19]  S. Maity,et al.  Phytochemistry, pharmacology, toxicology, and clinical trial of Ficus racemosa , 2015, Pharmacognosy reviews.

[20]  T. Xu,et al.  Gram-scale synthesis of single-crystalline graphene quantum dots with superior optical properties , 2014, Nature Communications.

[21]  E. Giannelis,et al.  Carbon dots—Emerging light emitters for bioimaging, cancer therapy and optoelectronics , 2014 .

[22]  H. Feng,et al.  Dual-colored graphene quantum dots-labeled nanoprobes/graphene oxide: functional carbon materials for respective and simultaneous detection of DNA and thrombin , 2014, Nanotechnology.

[23]  Chun‐Sing Lee,et al.  A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation , 2014, Nature Communications.

[24]  Z. Marković,et al.  Photodynamic antibacterial effect of graphene quantum dots. , 2014, Biomaterials.

[25]  K. Cen,et al.  Green preparation of reduced graphene oxide for sensing and energy storage applications , 2014, Scientific Reports.

[26]  Bingpo Zhang,et al.  Optical properties of pH-sensitive carbon-dots with different modifications , 2014 .

[27]  M. Sharon,et al.  Antibiotic Conjugated Fluorescent Carbon Dots as a Theranostic Agent for Controlled Drug Release, Bioimaging, and Enhanced Antimicrobial Activity , 2014, Journal of drug delivery.

[28]  Mei Jin,et al.  Cellular distribution and cytotoxicity of graphene quantum dots with different functional groups , 2014, Nanoscale Research Letters.

[29]  M. Sharon,et al.  Swarming carbon dots for folic acid mediated delivery of doxorubicin and biological imaging. , 2014, Journal of materials chemistry. B.

[30]  Jingyan Zhang,et al.  Insight into the Cellular Internalization and Cytotoxicity of Graphene Quantum Dots , 2013, Advanced healthcare materials.

[31]  Bai Yang,et al.  Self-assembled graphene quantum dots induced by cytochrome c: a novel biosensor for trypsin with remarkable fluorescence enhancement. , 2013, Nanoscale.

[32]  M. Sharon,et al.  Synthesis and Centrifugal Separation of Fluorescent Carbon Dots at Room Temperature , 2013 .

[33]  N. Mishra,et al.  Green synthesis of biocompatible carbon dots using aqueous extract of Trapa bispinosa peel. , 2013, Materials science & engineering. C, Materials for biological applications.

[34]  P. Oswald,et al.  Blinking effect and the use of quantum dots in single molecule spectroscopy. , 2013, Biochemical and biophysical research communications.

[35]  M. Swihart,et al.  In vivo toxicity of quantum dots: no cause for concern? , 2012, Nanomedicine.

[36]  Bai Yang,et al.  Surface Chemistry Routes to Modulate the Photoluminescence of Graphene Quantum Dots: From Fluorescence Mechanism to Up‐Conversion Bioimaging Applications , 2012 .

[37]  Zhenhui Kang,et al.  Carbon nanodots: synthesis, properties and applications , 2012 .

[38]  Djordje Klisic,et al.  Graphene quantum dots as autophagy-inducing photodynamic agents. , 2012, Biomaterials.

[39]  Guonan Chen,et al.  Blue luminescent graphene quantum dots and graphene oxide prepared by tuning the carbonization degree of citric acid , 2012 .

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

[41]  Siew Yee Wong,et al.  Intrinsically fluorescent carbon dots with tunable emission derived from hydrothermal treatment of glucose in the presence of monopotassium phosphate. , 2011, Chemical communications.

[42]  T. Desai,et al.  Pharmacognostic Study and Establishment of Quality Parameters of Leaves of Ficus racemosa Linn. , 2010 .

[43]  Huzhi Zheng,et al.  Study on the fluorescence characteristics of carbon dots. , 2010, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[44]  R. Nitschke,et al.  Quantum dots versus organic dyes as fluorescent labels , 2008, Nature Methods.

[45]  J. Bartek,et al.  Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. , 2004, DNA repair.

[46]  S. Mandal,et al.  Anti-inflammatory evaluation of Ficus racemosa Linn. leaf extract. , 2000, Journal of ethnopharmacology.

[47]  U. Schubert,et al.  Surface Chemistry of Planarized SiLK-Films Studied by XPS , 2000 .

[48]  T. Jacks,et al.  The cell cycle and cancer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[49]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[50]  Roopa Dharmatti,et al.  Synthesis of mesoporous silica oxide/C-dot complex (meso-SiO2/C-dots) using pyrolysed rice husk and its application in bioimaging , 2014 .

[51]  M. Sharon,et al.  A Green Route Towards Highly Photoluminescent and Cytocompatible Carbon dot Synthesis and its Separation Using Sucrose Density Gradient Centrifugation , 2014, Journal of Fluorescence.