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Biocompatible hyaluronic acid polymer-coated quantum dots for CD44+ cancer cell-targeted imaging

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Abstract

The cysteamine-modified hyaluronic acid (HA) polymer was employed to coat quantum dots (QDs) through a convenient one-step reverse micelle method, with the final QDs hydrodynamic size of around 22.6 nm. The HA coating renders the QDs with very good stability in PBS for more than 140 days and resistant to large pH range of 2–12. Besides, the HA-coated QDs also show excellent fluorescence stability in BSA-containing cell culture medium. In addition, the cell culture assay indicates no significant cytotoxicity for MD-MB-231 breast cancer cells, and its targeting ability to cancer receptor CD44 has been demonstrated on two breast cancer cell lines. The targeting mechanism was further proved by the HA competition experiment. This work has established a new approach to help solve the stability and toxicity problems of QDs, and moreover render the QDs cancer targeting property. The current results indicate that the HA polymer-coated QDs hold the potential application for both in vitro and in vivo cancer imaging researches.

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References

  • Britton HTS, Robinson RA (1931) CXCVIII.—Universal buffer solutions and the dissociation constant of veronal. J Chem Soc 1:1456–1462

    Article  Google Scholar 

  • Bruchez M, Moronne M, Gin P, Weiss S, Alivisatos AP (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016

    Article  Google Scholar 

  • Chan WCW, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018

    Article  Google Scholar 

  • Chan WCW, Maxwell DJ, Gao X, Bailey RE, Han M, Nie S (2002) Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotech 13:40–46

    Article  Google Scholar 

  • Chen B, Miller RJ, Dhal PK (2014) Hyaluronic acid-based drug conjugates: state-of-the-art and perspectives. J Biomed Nanotechnol 10:4–16

    Article  Google Scholar 

  • Cheng H-T, Chuang E-Y, Ma H, Tsai C-H, Perng C-K (2012) Fabrication of quantum dot-conjugated collagen/hyaluronic acid porous scaffold. Ann Plast Surg 69:663–667

    Article  Google Scholar 

  • Cheng Y, Zhao Y, Shangguan F, Ye B, Li T, Gu Z (2014) Convenient generation of quantum dot-incorporated photonic crystal beads for multiplex bioassays. J Biomed Nanotechnol 10:760–766

    Article  Google Scholar 

  • Cho SJ, Maysinger D, Jain M, Röder B, Hackbarth S, Winnik FM (2007) Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 23:1974–1980

    Article  Google Scholar 

  • Clapp AR, Goldman ER, Mattoussi H (2006) Capping of CdSe–ZnS quantum dots with DHLA and subsequent conjugation with proteins. Nat Protoc 1:1258–1266

    Article  Google Scholar 

  • Coradini D, Pellizzaro C, Miglierini G, Daidone MG, Perbellini A (1999) Hyaluronic acid as drug delivery for sodium butyrate: improvement of the anti-proliferative activity on a breast-cancer cell line. Int J Cancer 81:411–416

    Article  Google Scholar 

  • Derfus AM, Chan WC, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11–18

    Article  Google Scholar 

  • Duan HW, Kuang M, Wangi YA (2010) Quantum dots with multivalent and compact polymer coatings for efficient fluorescence resonance energy transfer and self-assembled biotagging. Chem Mat 22:4372–4378

    Article  Google Scholar 

  • Durgadas CV, Sreenivasan K, Sharma CP (2012) Bright blue emitting CuSe/ZnS/silica core/shell/shell quantum dots and their biocompatibility. Biomaterials 33:6420–6429

    Article  Google Scholar 

  • Gao X, Cui Y, Levenson RM, Chung LWK, Nie S (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976

    Article  Google Scholar 

  • Giovanelli E, Muro E, Sitbon G, Hanafi M, Pons T, Dubertret B, Lequeux N (2012) Highly enhanced affinity of multidentate versus bidentate zwitterionic ligands for long-term quantum dot bioimaging. Langmuir 28:15177–15184

    Article  Google Scholar 

  • Gold MH (2007) Use of hyaluronic acid fillers for the treatment of the aging face. Clin Interv Aging 2:369

    Google Scholar 

  • Hosseinkhani H, He W-J, Chiang C-H, Hong P-D, Yu D-S, Domb A, Ou K-L (2013) Biodegradable nanoparticles for gene therapy technology. J Nanopart Res 15:1–15

    Google Scholar 

  • Hu X, Gao X (2010) Silica-polymer dual layer-encapsulated quantum dots with remarkable stability. ACS Nano 4:6080–6086

    Article  Google Scholar 

  • Jana NR, Erathodiyil N, Jiang J, Ying JY (2010) Cysteine-functionalized polyaspartic acid: a polymer for coating and bioconjugation of nanoparticles and quantum dots. Langmuir 26:6503–6507

    Article  Google Scholar 

  • Jang YL et al (2014) Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery. J Nanosci Nanotechnol 14:7388–7394

    Article  Google Scholar 

  • Jiang G, Park K, Kim J, Kim KS, Hahn SK (2009) Target specific intracellular delivery of siRNA/PEI-HA complex by receptor mediated endocytosis. Mol Pharm 6:727–737

    Article  Google Scholar 

  • Kamat M, El-Boubbou K, Zhu DC, Lansdell T, Lu X, Li W, Huang X (2010) Hyaluronic acid immobilized magnetic nanoparticles for active targeting and imaging of macrophages. Bioconjugate Chem 21:2128–2135

    Article  Google Scholar 

  • Kerscher M, Bayrhammer J, Reuther T (2008) Rejuvenating influence of a stabilized hyaluronic acid-based gel of nonanimal origin on facial skin aging. Dermatol Surg 34:720–726

    Google Scholar 

  • Kim S-W, Kim S, Tracy JB, Jasanoff A, Bawendi MG (2005) Phosphine oxide polymer for water-soluble nanoparticles. J Am Chem Soc 127:4556–4557

    Article  Google Scholar 

  • Kim J et al (2008) In vivo real-time bioimaging of hyaluronic acid derivatives using quantum dots. Biopolymers 89:1144–1153

    Article  Google Scholar 

  • Kim KS, Kim S, Beack S, Yang JA, Yun SH, Hahn SK (2012) In vivo real time confocal microscopy for target specific delivery of hyaluronic acid-quantum dot conjugates. nanomedicine: nanotechnology. Biol Med 8:1070–1073

    Google Scholar 

  • Lee H, Mok H, Lee S, Oh YK, Park TG (2007) Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels. J Control Release 119:245–252

    Article  Google Scholar 

  • Leutwyler WK, Bürgi SL, Burgl H (1996) Semiconductor clusters, nanocrystals, and quantum dots. Science 271:933

    Article  Google Scholar 

  • Liu W, Choi HS, Zimmer JP, Tanaka E, Frangioni JV, Bawendi M (2007) Compact cysteine-coated CdSe (ZnCdS) quantum dots for in vivo applications. J Am Chem Soc 129:14530–14531

    Article  Google Scholar 

  • Liu W et al (2009) Compact biocompatible quantum dots via RAFT-mediated synthesis of imidazole-based random copolymer ligand. J Am Chem Soc 132:472–483

    Article  Google Scholar 

  • Liu L, Guo X, Li Y, Zhong X (2010) Bifunctional multidentate ligand modified highly stable water-soluble quantum dots. Inorg Chem 49:3768–3775

    Article  Google Scholar 

  • Lovrić J, Cho SJ, Winnik FM, Maysinger D (2005) Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem Biol 12:1227–1234

    Article  Google Scholar 

  • Luo Y, Prestwich GD (1999) Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugate. Bioconjugate Chem 10:755–763

    Article  Google Scholar 

  • Medintz IL, Uyeda HT, Goldman ER, Mattoussi H (2005) Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater 4:435–446

    Article  Google Scholar 

  • Palui G, Na HB, Mattoussi H (2011) Poly(ethylene glycol)-based multidentate oligomers for biocompatible semiconductor and gold nanocrystals. Langmuir 28:2761–2772

    Article  Google Scholar 

  • Pellegrino T et al (2004) Hydrophobic nanocrystals coated with an amphiphilic polymer shell: a general route to water soluble nanocrystals. Nano Lett 4:703–707

    Article  Google Scholar 

  • Platt VM, Szoka FC Jr (2008) Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Mol Pharm 5:474–486

    Article  Google Scholar 

  • Qu L, Peng X (2002) Control of photoluminescence properties of CdSe nanocrystals in growth. J Am Chem Soc 124:2049–2055

    Article  Google Scholar 

  • Ruan G, Agrawal A, Marcus AI, Nie S (2007) Imaging and tracking of tat peptide-conjugated quantum dots in living cells: new insights into nanoparticle uptake, intracellular transport, and vesicle shedding. J Am Chem Soc 129:14759–14766

    Article  Google Scholar 

  • Saravanakumar G, Deepagan V, Jayakumar R, Park JH (2014) Hyaluronic acid-based conjugates for tumor-targeted drug delivery and imaging. J Biomed Nanotechnol 10:17–31

    Article  Google Scholar 

  • Schroedter A, Weller H, Eritja R, Ford WE, Wessels JM (2002) Biofunctionalization of silica-coated CdTe and gold nanocrystals. Nano Lett 2:1363–1367

    Article  Google Scholar 

  • Shiohara A, Hoshino A, Hanaki Ki, Suzuki K, Yamamoto K (2004) On the cyto-toxicity caused by quantum dots. Microbiol Immunol 48:669–675

    Article  Google Scholar 

  • Smith AM, Nie S (2008) Minimizing the hydrodynamic size of quantum dots with multifunctional multidentate polymer ligands. J Am Chem Soc 130:11278–11279

    Article  Google Scholar 

  • Smith AM, Nie S (2011) Bright and compact alloyed quantum dots with broadly tunable near-infrared absorption and fluorescence spectra through mercury cation exchange. J Am Chem Soc 133:24

    Article  Google Scholar 

  • Smith AM, Duan H, Mohs AM, Nie S (2008a) Bioconjugated quantum dots for in vivo molecular and cellular imaging. Adv Drug Deliver Rev 60:1226–1240

    Article  Google Scholar 

  • Smith AM, Mohs AM, Nie S (2008b) Tuning the optical and electronic properties of colloidal nanocrystals by lattice strain. Nat Nanotechnol 4:56–63

    Article  Google Scholar 

  • Steponkiene S, Valanciunaite J, Skripka A, Rotomskis R (2014) Cellular uptake and photosensitizing properties of quantum dot-chlorin e 6 complex: in vitro study. J Biomed Nanotechnol 10:679–686

    Article  Google Scholar 

  • Stewart MH et al (2010) Multidentate poly(ethylene glycol) ligands provide colloidal stability to semiconductor and metallic nanocrystals in extreme conditions. J Am Chem Soc 132:9804–9813

    Article  Google Scholar 

  • Uskoković V, Drofenik M (2005) Synthesis of materials within reverse micelles. Surf Rev Lett 12:239–277

    Article  Google Scholar 

  • Wang TW, Sun JS, Wu HC, Tsuang YH, Wang WH, Lin FH (2006) The effect of gelatin-chondroitin sulfate-hyaluronic acid skin substitute on wound healing in SCID mice. Biomaterials 27:5689–5697

    Article  Google Scholar 

  • Wu X et al (2002) Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol 21:41–46

    Article  Google Scholar 

  • Wu YZ et al (2010) pH-Responsive quantum dots via an albumin polymer surface coating. J Am Chem Soc 132:5012–5014

    Article  Google Scholar 

  • Xie R, Kolb U, Li J, Basché T, Mews A (2005) Synthesis and characterization of highly luminescent CdSe-Core CdS/Zn0. 5Cd0. 5S/ZnS multishell nanocrystals. J Am Chem Soc 127:7480–7488

    Article  Google Scholar 

  • Xing Y et al (2007) Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry. Nat Protoc 2:1152–1165

    Article  Google Scholar 

  • Yadav AK, Mishra P, Agrawal GP (2008) An insight on hyaluronic acid in drug targeting and drug delivery. J Drug Target 16:91–107

    Article  Google Scholar 

  • Yildiz I, McCaughan B, Cruickshank SF, Callan JF, Raymo FiM (2009) Biocompatible CdSe-ZnS core-shell quantum dots coated with hydrophilic polythiols. Langmuir 25:7090–7096

    Article  Google Scholar 

  • Yildiz I, Deniz E, McCaughan B, Cruickshank SF, Callan JF, Raymo FiM (2010) Hydrophilic CdSe-ZnS core-shell quantum dots with reactive functional groups on their surface. Langmuir 26:11503–11511

    Article  Google Scholar 

  • Ying JY, Zarur A (2002) Synthesis of nanometer-sized particles by reverse micelle mediated techniques. US Patent 6,413,489

  • Zhang P et al (2012) Click-functionalized compact quantum dots protected by multidentate-imidazole ligands: conjugation-ready nanotags for living-virus labeling and imaging. J Am Chem Soc 134:8388–8391

    Article  Google Scholar 

  • Zheng H, Chen G, DeLouise LA, Lou Z (2010) Detection of the cancer marker CD146 expression in melanoma cells with semiconductor quantum dot label. J Biomed Nanotechnol 6:303–311

    Article  Google Scholar 

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Acknowledgments

We acknowledge the financial support by the Wallace H. Coulter GT/Emory-PKU BME collaborative research seed grant program and the National Key Instrumentation Development Project (2011YQ030114), as well as Guangdong Innovative Research Team Program (No. 2011S090). We also thank Dr. Andrew M. Smith for kindly providing the QDs.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Peking University, No.5 Yiheyuan Road, Haidian District, Beijing, 100871, People’s Republic of China

    Hening Wang, Hongfang Sun, Peng Xi & Qiushi Ren

  2. Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, Room E116, Atlanta, GA, 30322, USA

    Hening Wang, Hui Wei & Shuming Nie

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  1. Hening Wang
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  2. Hongfang Sun
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  5. Shuming Nie
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Correspondence to Shuming Nie or Qiushi Ren.

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Wang, H., Sun, H., Wei, H. et al. Biocompatible hyaluronic acid polymer-coated quantum dots for CD44+ cancer cell-targeted imaging. J Nanopart Res 16, 2621 (2014). https://doi.org/10.1007/s11051-014-2621-x

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