Fluorescent graphene quantum dots as traceable, pH-sensitive drug delivery systems

Graphene quantum dots (GQDs) were rationally fabricated as a traceable drug delivery system for the targeted, pH-sensitive delivery of a chemotherapeutic drug into cancer cells. The GQDs served as fluorescent carriers for a well-known anticancer drug, doxorubicin (Dox). The whole system has the capacity for simultaneous tracking of the carrier and of drug release. Dox release is triggered upon acidification of the intracellular vesicles, where the carriers are located after their uptake by cancer cells. Further functionalization of the loaded carriers with targeting moieties such as arginine-glycine-aspartic acid (RGD) peptides enhanced their uptake by cancer cells. DU-145 and PC-3 human prostate cancer cell lines were used to evaluate the anticancer ability of Dox-loaded RGD-modified GQDs (Dox-RGD-GQDs). The results demonstrated the feasibility of using GQDs as traceable drug delivery systems with the ability for the pH-triggered delivery of drugs into target cells.

[1]  S. Hurley,et al.  Multifunctional stable and pH-responsive polymer vesicles formed by heterofunctional triblock copolymer for targeted anticancer drug delivery and ultrasensitive MR imaging. , 2010, ACS nano.

[2]  M. P. Callao,et al.  Plasmonic nanoprobes for real-time optical monitoring of nitric oxide inside living cells. , 2013, Angewandte Chemie.

[3]  W. D. de Jong,et al.  Drug delivery and nanoparticles: Applications and hazards , 2008, International journal of nanomedicine.

[4]  H. Möhwald,et al.  Recent progress in morphology control of supramolecular fullerene assemblies and its applications. , 2010, Chemical Society reviews.

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

[6]  V. Préat,et al.  RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. , 2012, Molecular pharmaceutics.

[7]  Robert Langer,et al.  Impact of nanotechnology on drug delivery. , 2009, ACS nano.

[8]  Cyrille Boyer,et al.  Using fluorescence lifetime imaging microscopy to monitor theranostic nanoparticle uptake and intracellular doxorubicin release. , 2013, ACS nano.

[9]  Xin Huang,et al.  Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity , 2011 .

[10]  Vladimir P Torchilin,et al.  pH-sensitive poly(histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery. , 2013, Biomaterials.

[11]  R Langer,et al.  Responsive polymeric delivery systems. , 2001, Advanced drug delivery reviews.

[12]  James F Rusling,et al.  Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. , 2009, ACS nano.

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

[14]  Huaidong Jiang,et al.  In vitro investigation on the biodegradability and biocompatibility of genipin cross-linked porcine acellular dermal matrix with intrinsic fluorescence. , 2013, ACS applied materials & interfaces.

[15]  W. Parak,et al.  pH-sensitive capsules as intracellular optical reporters for monitoring lysosomal pH changes upon stimulation. , 2012, Small.

[16]  Ji Won Suk,et al.  Graphene and Graphene Oxide: Synthesis, Properties, and Applications , 2010 .

[17]  F. Braet,et al.  Carbon Nanomaterials in Biosensors: Should You Use Nanotubes or Graphene? , 2010 .

[18]  Z. Yin,et al.  Magnetite nanoparticles as smart carriers to manipulate the cytotoxicity of anticancer drugs: magnetic control and pH-responsive release , 2012 .

[19]  Baoan Chen,et al.  Daunorubicin-TiO2 nanocomposites as a “smart” pH-responsive drug delivery system , 2011, International journal of nanomedicine.

[20]  R. Misra,et al.  Controlled release of drug from folate-decorated and graphene mediated drug delivery system: Synthesis, loading efficiency, and drug release response , 2011 .

[21]  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.

[22]  Raimo Hartmann,et al.  Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge , 2012, Journal of Nanobiotechnology.

[23]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

[24]  Kumar,et al.  Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon , 2012, International journal of nanomedicine.

[25]  Yongsheng Chen,et al.  High-Efficiency Loading and Controlled Release of Doxorubicin Hydrochloride on Graphene Oxide , 2008 .

[26]  Andre K. Geim,et al.  The rise of graphene. , 2007, Nature materials.

[27]  Philip S Low,et al.  Folate-mediated delivery of macromolecular anticancer therapeutic agents. , 2002, Advanced drug delivery reviews.

[28]  M. Endo,et al.  Carbon nanotubes: biomaterial applications. , 2009, Chemical Society reviews.

[29]  T. K. Maiti,et al.  Perylene-3-ylmethanol: fluorescent organic nanoparticles as a single-component photoresponsive nanocarrier with real-time monitoring of anticancer drug release. , 2012, Journal of the American Chemical Society.

[30]  Jun Jie Wang,et al.  Recent advances of chitosan nanoparticles as drug carriers , 2011, International journal of nanomedicine.

[31]  A. Seifalian,et al.  A new era of cancer treatment: carbon nanotubes as drug delivery tools , 2011, International journal of nanomedicine.

[32]  Fang Liu,et al.  Strongly green-photoluminescent graphene quantum dots for bioimaging applications. , 2011, Chemical communications.

[33]  Xiaoling Yang,et al.  Graphene quantum dots: emergent nanolights for bioimaging, sensors, catalysis and photovoltaic devices. , 2012, Chemical communications.

[34]  Shuk Han Cheng,et al.  Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells , 2011, International journal of nanomedicine.

[35]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

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

[37]  Pavel Zrazhevskiy,et al.  Quantum dots as a platform for nanoparticle drug delivery vehicle design. , 2013, Advanced drug delivery reviews.

[38]  Xiaohu Gao,et al.  Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. , 2010, Chemical Society reviews.

[39]  Ru Jiang,et al.  Preparation, characterization, and in vitro targeted delivery of folate-decorated paclitaxel-loaded bovine serum albumin nanoparticles , 2010, International journal of nanomedicine.

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

[41]  You Han Bae,et al.  Recent progress in tumor pH targeting nanotechnology. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[42]  V. Biju Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. , 2014, Chemical Society reviews.

[43]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .