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Multifunctional nanosheets based on hyaluronic acid modified graphene oxide for tumor-targeting chemo-photothermal therapy

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Abstract

Graphene oxide (GO) with strong optical absorption in the near-infrared (NIR) region has shown great potential both in photothermal therapy and drug delivery. In this work, hyaluronic acid (HA)-functionalized GO (HA-GO) was successfully synthesized and controlled loading of mitoxantrone (MIT) onto HA-GO via π–π stacking interaction was investigated. The results revealed that drug-loaded nanosheets with high loading efficiency of 45 wt% exhibited pH-sensitive responses to tumor environment. Owing to the receptor-mediated endocytosis, cellular uptake analysis of HA-GO showed enhanced internalization. In vivo optical imaging test demonstrated that HA-GO nanosheets could enhance the targeting ability and residence time in tumor site. Moreover, the anti-tumor activity of free MIT, MIT/GO, and MIT/HA-GO in combination with NIR laser was investigated using human MCF-7 cells. In vitro cytotoxicity study revealed that HA-GO could stand as a biocompatible nanocarrier and MIT/HA-GO demonstrated remarkably higher toxicity than free MIT and MIT/GO, with IC50 of 0.79 µg ml−1. Tumor cell-killing potency was enhanced when MIT/HA-GO were combined with NIR irradiation, and the IC50 of MIT/HA-GO plus laser irradiation was 0.38 µg ml−1. In vivo, MIT/HA-GO plus NIR laser irradiation with the tumor growth inhibition of 93.52 % displayed greater anti-tumor effect compared with free MIT and MIT/GO with or without laser irradiation. Therefore, the MIT/HA-GO nanosheets may potentially be useful for further development of synergistic cancer therapy.

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References

  • Adachi S, Kokura S, Okayama T, Ishikawa T, Takagi T, Handa O, Naito Y, Yoshikawa T (2009) Effect of hyperthermia combined with gemcitabine on apoptotic cell death in cultured human pancreatic cancer cell lines. Int J Hyperth 25:210–219

    Article  Google Scholar 

  • An G, Morris ME (2010) HPLC analysis of mitoxantrone in mouse plasma and tissues: application in a pharmacokinetic study. J Pharm Biomed Anal 51:750–753

    Article  Google Scholar 

  • Boca SC, Potara M, Gabudean A-M, Juhem A, Baldeck PL, Astilean S (2011) Chitosan-coated triangular silver nanoparticles as a novel class of biocompatible, highly effective photothermal transducers for in vitro cancer cell therapy. Cancer Lett 311:131–140

    Article  Google Scholar 

  • Cho YW, Park SA, Han TH, Son DH, Park JS, Oh SJ, Moon DH, Cho KJ, Ahn CH, Byun Y et al (2007) In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications. Biomaterials 28:1236–1247

    Article  Google Scholar 

  • Choi KY, Chung H, Min KH, Yoon HY, Kim K, Park JH, Kwon IC, Jeong SY (2010) Self-assembled hyaluronic acid nanoparticles for active tumor targeting. Biomaterials 31:106–114

    Article  Google Scholar 

  • Entwistle J, Hall CL, Turley EA (1996) HA receptors: regulators of signalling to the cytoskeleton. J Cell Biochem 61:569–577

    Article  Google Scholar 

  • Gillies ER, Frechet JM (2005) pH-responsive copolymer assemblies for controlled release of doxorubicin. Bioconjug Chem 16:361–368

    Article  Google Scholar 

  • He X, Wolkers WF, Crowe JH, Swanlund DJ, Bischof JC (2004) In situ thermal denaturation of proteins in dunning AT-1 prostate cancer cells: implication for hyperthermic cell injury. Ann Biomed Eng 32:1384–1398

    Article  Google Scholar 

  • He M, Zhao Z, Yin L, Tang C, Yin C (2009) Hyaluronic acid coated poly(butyl cyanoacrylate) nanoparticles as anticancer drug carriers. Int J Pharm 373:165–173

    Article  Google Scholar 

  • Hou L, Yao J, Zhou J, Zhang Q (2012) Pharmacokinetics of a paclitaxel-loaded low molecular weight heparin-all-trans-retinoid acid conjugate ternary nanoparticulate drug delivery system. Biomaterials 33:5431–5440

    Article  Google Scholar 

  • Huang P, Xu C, Lin J, Wang C, Wang X, Zhang C, Zhou X, Guo S, Cui D (2011) Folic acid-conjugated graphene oxide loaded with photosensitizers for targeting photodynamic therapy. Theranostics 1:240–250

    Article  Google Scholar 

  • Liang C, Li H, Wang L, Chen X, Zhao W (2010) Investigation of the cytotoxicity of carbon nanotubes using hydroxyapatite as a nano-matrix towards mouse fibroblast cells. Mater Chem Phys 124:21–24

    Article  Google Scholar 

  • Liu J, Ohta S, Sonoda A, Yamada M, Yamamoto M, Nitta N, Murata K, Tabata Y (2007) Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy. J Control Release 117:104–110

    Article  Google Scholar 

  • Liu H, Chen D, Li L, Liu T, Tan L, Wu X, Tang F (2011a) Multifunctional gold nanoshells on silica nanorattles: a platform for the combination of photothermal therapy and chemotherapy with low systemic toxicity. Angew Chem Int Ed Engl 50:891–895

    Article  Google Scholar 

  • Liu X, Tao H, Yang K, Zhang S, Lee S-T, Liu Z (2011b) Optimization of surface chemistry on single-walled carbon nanotubes for in vivo photothermal ablation of tumors. Biomaterials 32:144–151

    Article  Google Scholar 

  • Liu H, Liu T, Wu X, Li L, Tan L, Chen D, Tang F (2012) Targeting gold nanoshells on silica nanorattles: a drug cocktail to fight breast tumors via a single irradiation with near-infrared laser light. Adv Mater 24:755–761

    Article  Google Scholar 

  • Melancon MP, Elliott AM, Shetty A, Huang Q, Stafford RJ, Li C (2011a) Near-infrared light modulated photothermal effect increases vascular perfusion and enhances polymeric drug delivery. J Control Release 156:265–272

    Article  Google Scholar 

  • Melancon MP, Lu W, Zhong M, Zhou M, Liang G, Elliott AM, Hazle JD, Myers JN, Li C, Stafford RJ (2011b) Targeted multifunctional gold-based nanoshells for magnetic resonance-guided laser ablation of head and neck cancer. Biomaterials 32:7600–7608

    Article  Google Scholar 

  • Meng L, Zhang X, Lu Q, Fei Z, Dyson PJ (2012) Single walled carbon nanotubes as drug delivery vehicles: targeting doxorubicin to tumors. Biomaterials 33:1689–1698

    Article  Google Scholar 

  • Qin XC, Guo ZY, Liu ZM, Zhang W, Wan MM, Yang BW (2013) Folic acid-conjugated graphene oxide for cancer targeted chemo-photothermal therapy. J Photochem Photobiol B 120:156–162

    Article  Google Scholar 

  • Robinson JT, Tabakman SM, Liang Y, Wang H, Casalongue HS, Vinh D, Dai H (2011) Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. J Am Chem Soc 133:6825–6831

    Article  Google Scholar 

  • Shan C, Yang H, Han D, Zhang Q, Ivaska A, Niu L (2009) Water-soluble graphene covalently functionalized by biocompatible poly-l-lysine. Langmuir 25:12030–12033

    Article  Google Scholar 

  • Sun X, Liu Z, Welsher K, Robinson JT, Goodwin A, Zaric S, Dai H (2008) Nano-graphene oxide for cellular imaging and drug delivery. Nano Res 1:203–212

    Article  Google Scholar 

  • Tian B, Wang C, Zhang S, Feng L, Liu Z (2011) Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano 5:7000–7009

    Article  Google Scholar 

  • Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JF, Farooque A, Chandraiah G, Jain AK et al (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamma-benzyl l-glutamate)-b-hyaluronan polymersomes. Biomaterials 31:2882–2892

    Article  Google Scholar 

  • Yang X, Zhang X, Liu Z, Ma Y, Huang Y, Chen Y (2008) High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J Phys Chem C 112:17554–17558

    Article  Google Scholar 

  • Yang K, Zhang S, Zhang G, Sun X, Lee ST, Liu Z (2010) Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett 10:3318–3323

    Article  Google Scholar 

  • You J, Zhang R, Zhang G, Zhong M, Liu Y, Van Pelt CS, Liang D, Wei W, Sood AK, Li C (2012) Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: a platform for near-infrared light-trigged drug release. J Control Release 158:319–328

    Article  Google Scholar 

  • Zhang L, Xia J, Zhao Q, Liu L, Zhang Z (2010a) Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small 6:537–544

    Article  Google Scholar 

  • Zhang Y, Ali SF, Dervishi E, Xu Y, Li Z, Casciano D, Biris AS (2010b) Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano 4:3181–3186

    Article  Google Scholar 

  • Zhang W, Guo Z, Huang D, Liu Z, Guo X, Zhong H (2011) Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. Biomaterials 32:8555–8561

    Article  Google Scholar 

  • Zhu Y, Murali S, Cai W, Li X, Suk JW, Potts JR, Ruoff RS (2010) Graphene and graphene oxide: synthesis, properties, and applications. Adv Mater 22:3906–3924

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (81202485 and 81273451).

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    Authors and Affiliations

    1. School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, China

      Lin Hou, Qianhua Feng, Yating Wang, Huijuan Zhang, Guixiang Jiang, Xiaomin Yang, Junxiao Ren, Xiali Zhu, Yuyang Shi & Zhenzhong Zhang

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    1. Lin Hou
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    2. Qianhua Feng
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    3. Yating Wang
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    Correspondence to Zhenzhong Zhang.

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    Lin Hou and Qianhua Feng have contributed equally to this work.

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    Hou, L., Feng, Q., Wang, Y. et al. Multifunctional nanosheets based on hyaluronic acid modified graphene oxide for tumor-targeting chemo-photothermal therapy. J Nanopart Res 17, 162 (2015). https://doi.org/10.1007/s11051-015-2966-9

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