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Facile synthesis of near-infrared CuInS2/ZnS quantum dots and glycol-chitosan coating for in vivo imaging

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Abstract

This study describes the synthesis method of water-soluble, low-toxicity, photostable highly luminescent probes based on I–III–VI2 type semiconductor quantum dots (QDs) and the possibility of tumor targeting in living animals. Cd-free high-quality CuInS2/ZnS core/shell QDs were synthesized, and their surfaces were reacted with mercaptoundecanoic acid for aqueous phase transfer followed by reaction with glycol-chitosan; lastly, Arg-Gly-Asp (RGD) integrin-binding peptide was covalently attached for in vivo tumor targeting. Dowtherm A, a highly viscous heat-transfer organic fluid, was used to control semiconductor crystal growth at high temperature (>230 °C) during organic synthesis. The structural and optical properties of the resulting CuInS2/ZnS QDs were investigated. The average diameters of CuInS2 and CuInS2/ZnS QDs were 3.0 and 3.7 nm, respectively. Cell toxicity and in vivo tumor targetability in RR1022 cancer cell-xenografted mice were further evaluated using cRGDyk-tagged glycol-chitosan-coated CuInS2/ZnS QDs. Glycol-chitosan-coated MUA-QDs displayed a Z-average diameter of 203.8 ± 7.67 nm in water by dynamic light scattering.

In vivo tumor targeting using cRGDyk-tagged glycol-chitosan-coated MUA-CuInS2/ZnS QDs nanoparticles

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References

  • Antonov AS, Kolodgie FD, Munn DH, Gerrity RG (2004) Regulation of macrophage foam cell formation by alphaVbeta3 integrin: potential role in human atherosclerosis. Am J Pathol 165(1):247–258. doi:10.1016/S0002-9440(10)63293-2

    Article  Google Scholar 

  • Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8(8):604–617. doi:10.1038/nrc2353

    Article  Google Scholar 

  • Bajaj G, Van Alstine WG, Yeo Y (2012) Zwitterionic chitosan derivative, a new biocompatible pharmaceutical excipient, prevents endotoxin-mediated cytokine release. PLoS One 7(1):e30899. doi:10.1371/journal.pone.0030899

    Article  Google Scholar 

  • Brunetti V, Chibli H, Fiammengo R, Galeone A, Malvindi MA, Vecchio G et al (2013) InP/ZnS as a safer alternative to CdSe/ZnS core/shell quantum dots: in vitro and in vivo toxicity assessment. Nano 5(1):307–317. doi:10.1039/c2nr33024e

    Google Scholar 

  • Chen CW, Wu DY, Chan YC, Lin CC, Chung PH, Hsiao M et al (2015) Evaluations of the chemical stability and cytotoxicity of CuInS2 and CuInS2/ZnS core/shell quantum dots. J Phys Chem C 119(5):2852–2860. doi:10.1021/jp510908f

    Article  Google Scholar 

  • Chen HJ, Niu G, Wu H, Chen XY (2016) Clinical application of radiolabeled RGD peptides for PET imaging of integrin alpha(v)beta(3). Theranostics 6(1):78–92. doi:10.7150/thno.13242

    Article  Google Scholar 

  • Deng DW, Chen YQ, Cao J, Tian JM, Qian ZY, Achilefu S et al (2012) High-quality CuInS2/ZnS quantum dots for in vitro and in vivo bioimaging. Chem Mater 24(15):3029–3037. doi:10.1021/cm3015594

    Article  Google Scholar 

  • Fu M, Luan W, Tu ST, Mleczko L (2015) Green synthesis of CuInS2/ZnS nanocrystals with high photoluminescence and stability. J Nanomater 842365. doi:10.1155/2015/842365

  • Guo W, Chen N, Tu Y, Dong C, Zhang B, Hu C et al (2013) Synthesis of Zn-Cu-In-S/ZnS core/shell quantum dots with inhibited blue-shift photoluminescence and applications for tumor targeted bioimaging. Theranostics 3(2):99–108. doi:10.7150/thno.5361

    Article  Google Scholar 

  • Helle M, Cassette E, Bezdetnaya L, Pons T, Leroux A, Plenat F et al (2012) Visualisation of sentinel lymph node with indium-based near infrared emitting quantum dots in a murine metastatic breast cancer model. PLoS One 7(8):e44433. doi:10.1371/journal.pone.0044433

    Article  Google Scholar 

  • Hyung Park J, Kwon S, Lee M, Chung H, Kim JH, Kim YS et al (2006) Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity. Biomaterials 27(1):119–126. doi:10.1016/j.biomaterials.2005.05.028

    Article  Google Scholar 

  • Kitagawa T, Kosuge H, Uchida M, Dua MM, Iida Y, Dalman RL et al (2012) RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease. Mol Imaging Biol 14(3):315–324. doi:10.1007/s11307-011-0495-1

    Article  Google Scholar 

  • Lee J, Han CS (2015) Bright, stable, and water-soluble CuInS2/ZnS nanocrystals passivated by cetyltrimethylammonium bromide. Nanoscale Res Lett 10:145. doi:10.1186/S11671-015-0836-0

    Article  Google Scholar 

  • Li LA, Pandey A, Werder DJ, Khanal BP, Pietryga JM, Klimov VI (2011) Efficient synthesis of highly luminescent copper indium sulfide-based core/shell nanocrystals with surprisingly long-lived emission. J Am Chem Soc 133(5):1176–1179. doi:10.1021/ja108261h

    Article  Google Scholar 

  • Li L, Daou TJ, Texier I, Tran TKC, Nguyen QL, Reiss P (2009) Highly luminescent CuInS2/ZnS core/shell nanocrystals: cadmium-free quantum dots for in vivo imaging. Chem Mater 21(12):2422–2429. doi:10.1021/cm900103b

    Article  Google Scholar 

  • Lim CH, Han JH, Cho HW, Kang M (2014) Studies on the toxicity and distribution of indium compounds according to particle size in Sprague-Dawley rats. Toxicol Res 30(1):55–63. doi:10.5487/TR.2014.30.1.055

    Article  Google Scholar 

  • Liu SY, Zhang H, Qiao Y, Su XG (2012) One-pot synthesis of ternary CuInS2 quantum dots with near-infrared fluorescence in aqueous solution. RSC Adv 2:819–825. doi:10.1039/c1ra00802a

    Article  Google Scholar 

  • Na JH, Koo H, Lee S, Min KH, Park K, Yoo H et al (2011) Real-time and non-invasive optical imaging of tumor-targeting glycol chitosan nanoparticles in various tumor models. Biomaterials 32(22):5252–5261. doi:10.1016/j.biomaterials.2011.03.076

    Article  Google Scholar 

  • Na JH, Lee SY, Lee S, Koo H, Min KH, Jeong SY et al (2012) Effect of the stability and deformability of self-assembled glycol chitosan nanoparticles on tumor-targeting efficiency. J Control Release 163(1):2–9. doi:10.1016/j.jconrel.2012.07.028

    Article  Google Scholar 

  • Najafabadi AH, Abdouss M, Faghihi S (2014a) Synthesis and evaluation of PEG-O-chitosan nanoparticles for delivery of poor water soluble drugs: ibuprofen. Mater Sci Eng C Mater Biol Appl 41:91–99. doi:10.1016/j.msec.2014.04.035

    Article  Google Scholar 

  • Najafabadi AH, Abdouss M, Faghihi S (2014b) Preparation and characterization of PEGylated chitosan nanocapsules as a carrier for pharmaceutical application. J Nanopart Res 16(3):2312. doi:10.1007/S11051-014-2312-7

    Article  Google Scholar 

  • Najafabadi AH, Azodi-Deilami S, Abdouss M, Payravand H, Farzaneh S (2015) Synthesis and evaluation of hydroponically alginate nanoparticles as novel carrier for intravenous delivery of propofol. J Mater Sci Mater Med 26(3):145. doi:10.1007/S10856-015-5452-0

    Article  Google Scholar 

  • Nakamura H, Kato W, Uehara M, Nose K, Omata T, Otsuka-Yao-Matsuo S et al (2006) Tunable photoluminescence wavelength of chalcopyrite CuInS2-based semiconductor nanocrystals synthesized in a colloidal system. Chem Mater 18(14):3330–3335. doi:10.1021/cm0518022

    Article  Google Scholar 

  • Niu G, Chen X (2011) Why integrin as a primary target for imaging and therapy. Theranostics 1:30–47. doi:10.7150/thno/v01p0030

    Article  Google Scholar 

  • Panthani MG, Akhavan V, Goodfellow B, Schmidtke JP, Dunn L, Dodabalapur A et al (2008) Synthesis of CuInS2, CuInSe2, and Cu(InxGa1-x)Se-2 (CIGS) nanocrystal “inks” for printable photovoltaics. J Am Chem Soc 130(49):16770–16777. doi:10.1021/ja805845q

    Article  Google Scholar 

  • Pons T, Pic E, Lequeux N, Cassette E, Bezdetnaya L, Guillemin F et al (2010) Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity. ACS Nano 4(5):2531–2538. doi:10.1021/nn901421v

    Article  Google Scholar 

  • Qi KZ, Wang Y, Wang RD, Wu D, Li GD (2016) Facile synthesis of homogeneous CuInS2 quantum dots with tunable near-infrared emission. J Mater Chem C 4:1895–1899. doi:10.1039/c5tc04232a

    Article  Google Scholar 

  • Ristig S, Kozlova D, Meyer-Zaika W, Epple M (2014) An easy synthesis of autofluorescent alloyed silver-gold nanoparticles. J Mater Chem B 2:7887–7895. doi:10.1039/c4tb01010h

    Article  Google Scholar 

  • Riva R, Ragelle H, des Rieux A, Duhem N, Jerome C, Preat V (2011) Chitosan and chitosan derivatives in drug delivery and tissue engineering. Adv Polym Sci 244:19–44. doi: 10.1007/12_2011_137

  • Speranskaya ES, Sevrin C, De Saeger S, Hens Z, Goryacheva IY, Grandfils C (2016) Synthesis of hydrophilic CuInS2/ZnS quantum dots with different polymeric shells and study of their cytotoxicity and hemocompatibility. ACS Appl Mater Interfaces 8(12):7613–7622. doi:10.1021/acsami.5b11258

    Article  Google Scholar 

  • Tang R, Xue J, Xu B, Shen D, Sudlow GP, Achilefu S (2015) Tunable ultrasmall visible-to-extended near-infrared emitting silver sulfide quantum dots for integrin-targeted cancer imaging. ACS Nano 9(1):220–230. doi:10.1021/nn5071183

    Article  Google Scholar 

  • Vancraeynest D, Roelants V, Bouzin C, Hanin FX, Walrand S, Bol V et al (2016) αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice. EJNMMI 6(1):29. doi:10.1186/s13550-016-0184-9

    Article  Google Scholar 

  • Xie BB, Hu BB, Jiang LF, Li G, Du ZL (2015) The phase transformation of CuInS2 from chalcopyrite to wurtzite. Nanoscale Res Lett 10:86. doi:10.1186/s11671-015-0800-z

    Article  Google Scholar 

  • Xie R, Rutherford M, Peng X (2009) Formation of high-quality I-III-VI semiconductor nanocrystals by tuning relative reactivity of cationic precursors. J Am Chem Soc 131(15):5691–5697. doi:10.1021/ja9005767

    Article  Google Scholar 

  • Yong KT, Roy I, Hu R, Ding H, Cai HX, Zhu J et al (2010) Synthesis of ternary CuInS2/ZnS quantum dot bioconjugates and their applications for targeted cancer bioimaging. Integr Biol 2(2–3):121–129. doi:10.1039/b916663g

    Article  Google Scholar 

  • Yoon HY, Son S, Lee SJ, You DG, Yhee JY, Park JH et al (2014) Glycol chitosan nanoparticles as specialized cancer therapeutic vehicles: sequential delivery of doxorubicin and Bcl-2 siRNA. Sci Rep 4:6878. doi:10.1038/Srep06878

    Article  Google Scholar 

  • Yu C, Zhang LL, Tian L, Liu D, Chen FL, Wang C (2014) Synthesis and formation mechanism of CuInS2 nanocrystals with a tunable phase. CrystEngComm 16:9596–9602. doi:10.1039/c4ce00893f

    Article  Google Scholar 

  • Zang H, Li H, Makarov NS, Velizhanin KA, Wu K, Park YS et al (2017) Thick-shell CuInS2/ZnS quantum dots with suppressed “blinking” and narrow single-particle emission line widths. Nano Lett 17(3):1787–1795. doi:10.1021/acs.nanolett.6b05118

    Article  Google Scholar 

  • Zhang JB, Sun WP, Yin LP, Miao XS, Zhang DL (2014) One-pot synthesis of hydrophilic CuInS2 and CuInS2-ZnS colloidal quantum dots. J Mater Chem C 2:4812–4817. doi:10.1039/c3tc32564d

    Article  Google Scholar 

  • Zhang RL, Yang P, Wang YQ (2013) Facile synthesis of CuInS2/ZnS quantum dots with highly near-infrared photoluminescence via phosphor-free process. J Nanopart Res 15:1910. doi:10.1007/S11051-013-1910-0

    Article  Google Scholar 

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Acknowledgements

This work was supported by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (2015M2A2A6A04044884 and 2016M2A2A7A03912640).

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Correspondence to Hwan-Jeong Jeong.

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Kim, EM., Lim, S.T., Sohn, MH. et al. Facile synthesis of near-infrared CuInS2/ZnS quantum dots and glycol-chitosan coating for in vivo imaging. J Nanopart Res 19, 251 (2017). https://doi.org/10.1007/s11051-017-3944-1

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