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X-ray microscopy and tomography detect the accumulation of bare and PEG-coated gold nanoparticles in normal and tumor mouse tissues

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Abstract

We demonstrate that, with appropriate staining, high-resolution X-ray microscopy can image complicated tissue structures—cerebellum and liver—and resolve large or small amounts of Au nanoparticles in these tissues. Specifically, images of tumor tissue reveal high concentrations of accumulated Au nanoparticles. PEG (poly(ethylene glycol)) coating is quite effective in enhancing this accumulation and significantly modifies the mechanism of uptake by reticuloendothelial system (RES) organs.

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References

  1. Kim D, Jeong YY, Jon S (2010) A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano 4:3689–3696

    Article  CAS  Google Scholar 

  2. Rothenfluh DA, Bermudez H, O'Neil CP, Hubbell JA (2008) Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. Nat Mater 7:248–254

    Article  CAS  Google Scholar 

  3. Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S (2009) Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery. Biomaterials 30:6065–6075

    Article  CAS  Google Scholar 

  4. Popovtzer R, Agrawal A, Kotov NA, Popovtzer A, Balter J, Carey TE, Kopelman R (2008) Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer. Nano Lett 8:4593–4596

    Article  CAS  Google Scholar 

  5. Chien CC, Kempson IM, Wang CL, Chen HH, Hwu Y, Chen NY, Lee TK, Petibois C, Tsai KK, Liu MS, Chang KY, Yang CS, Margaritondo G (2011) Complete microscale profiling of tumor microangiogenesis A microradiological methodology reveals fundamental aspects of tumor angiogenesis and yields an array of quantitative parameters for its characterization. Biotechnol Adv. doi:10.1016/j.biotechadv.2011.12.001

  6. Chien CC, Wang CH, Wang CL, Li ER, Lee KH, Hwu Y, Lin CY, Chang SJ, Yang CS, Petibois C, Margaritondo G (2010) Synchrotron microangiography studies of angiogenesis in mice with microemulsions and gold nanoparticles. Anal Bioanal Chem 397:2109–2116

    Article  CAS  Google Scholar 

  7. Au L, Chen J, Wang LV, Xia Y (2010) Gold nanocages for cancer imaging and therapy. Methods Mol Biol 624:83–99

    Article  CAS  Google Scholar 

  8. Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56:1649–1659

    Article  CAS  Google Scholar 

  9. Chien CC, Wang CH, Hua TE, Tseng PY, Yang TY, Hwu Y, Chen YJ, Chung KH, Je JH, Margaritondo G (2007) Synchrotron x-ray synthesized gold nanoparticles for tumor therapy. In: Choi JY, Rah S (eds) Synchrotron Radiation Instrumentation, Pts 1 and 2, vol 879. AIP Conference Proceedings. American Institute of Physics, New York, pp 1908–1911

  10. Chen HH, Chien CC, Petibois C, Wang CL, Chu YS, Lai SF, Hua TE, Chen YY, Cai X, Kempson IM, Hwu Y, Margaritondo G (2011) Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy. J Nanobiotechnology 9:14

    Article  CAS  Google Scholar 

  11. Chu YS, Yi JM, De Carlo F, Shen Q, Lee WK, Wu HJ, Wang CL, Wang JY, Liu CJ, Wang CH, Wu SR, Chien CC, Hwu Y, Tkachuk A, Yun W, Feser M, Liang KS, Yang CS, Je JH, Margaritondo G (2008) Hard-x-ray microscopy with Fresnel zone plates reaches 40 nm Rayleigh resolution. Appl Phys Lett 92:103119

    Article  Google Scholar 

  12. Chen YT, Chen TY, Yi JM, Chu YS, Lee WK, Wang CL, Kempson IM, Hwu Y, Gajdosik V, Margaritondo G (2011) Hard x-ray Zernike microscopy reaches 30 nm resolution. Opt Lett 36:1269–1271

    Article  Google Scholar 

  13. Chen YT, Lo TN, Chu YS, Yi J, Liu CJ, Wang JY, Wang CL, Chiu CW, Hua TE, Hwu Y, Shen Q, Yin GC, Liang KS, Lin HM, Je JH, Margaritondo G (2008) Full-field hard x-ray microscopy below 30 nm: a challenging nanofabrication achievement. Nanotechnology 19:395302

    Article  Google Scholar 

  14. Chen TY, Chen YT, Wang CL, Kempson IM, Lee WK, Chu YS, Hwu Y, Margaritondo G (2011) Full-field microimaging with 8 keV X-rays achieves a spatial resolutions better than 20 nm. Opt Express 19:19919–19924

    Article  Google Scholar 

  15. Meuli R, Hwu Y, Je JH, Margaritondo G (2004) Synchrotron radiation in radiology: radiology techniques based on synchrotron sources. Eur Radiol 14:1550–1560

    Article  Google Scholar 

  16. Hwu Y, Tsai WL, Chang HM, Yeh HI, Hsu PC, Yang YC, Su YT, Tsai HL, Chow GM, Ho PC, Li SC, Moser HO, Yang P, Seol SK, Kim CC, Je JH, Stefanekova E, Groso A, Margaritondo G (2004) Imaging cells and tissues with refractive index radiology. Biophys J 87:4180–4187

    Article  CAS  Google Scholar 

  17. Sharma P, Singh A, Brown SC, Bengtsson N, Walter GA, Grobmyer SR, Iwakuma N, Santra S, Scott EW, Moudgil BM (2010) Multimodal nanoparticulate bioimaging contrast agents. Methods Mol Biol 624:67–81

    Article  CAS  Google Scholar 

  18. Lu S, Xu X, Zhao W, Wu W, Yuan H, Shen H, Zhou C, Li LS, Ma L (2010) Targeting of embryonic stem cells by peptide-conjugated quantum dots. PLoS One 5:e12075

    Article  Google Scholar 

  19. Schluep T, Hwang J, Hildebrandt IJ, Czernin J, Choi CH, Alabi CA, Mack BC, Davis ME (2009) Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements. Proc Natl Acad Sci U S A 106:11394–11399

    Article  CAS  Google Scholar 

  20. Smirnov P, Lavergne E, Gazeau F, Lewin M, Boissonnas A, Doan BT, Gillet B, Combadiere C, Combadiere B, Clement O (2006) In vivo cellular imaging of lymphocyte trafficking by MRI: a tumor model approach to cell-based anticancer therapy. Magn Reson Med 56:498–508

    Article  CAS  Google Scholar 

  21. Bui T, Stevenson J, Hoekman J, Zhang S, Maravilla K, Ho RJ (2010) Novel Gd nanoparticles enhance vascular contrast for high-resolution magnetic resonance imaging. PLoS One 5:e13082

    Article  Google Scholar 

  22. Markov DE, Boeve H, Gleich B, Borgert J, Antonelli A, Sfara C, Magnani M (2010) Human erythrocytes as nanoparticle carriers for magnetic particle imaging. Phys Med Biol 55:6461–6473

    Article  CAS  Google Scholar 

  23. Tholouli E, Sweeney E, Barrow E, Clay V, Hoyland JA, Byers RJ (2008) Quantum dots light up pathology. J Pathol 216:275–285

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Niidome T, Akiyama Y, Shimoda K, Kawano T, Mori T, Katayama Y, Niidome Y (2008) In vivo monitoring of intravenously injected gold nanorods using near-infrared light. Small 4:1001–1007

    Article  CAS  Google Scholar 

  26. Hahn MA, Singh AK, Sharma P, Brown SC, Moudgil BM (2010) Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives. Anal Bioanal Chem 399:3–27

    Article  Google Scholar 

  27. Liu CJ, Wang CH, Chien CC, Yang TY, Chen ST, Leng WH, Lee CF, Lee KH, Hwu Y, Lee YC, Cheng CL, Yang CS, Chen YJ, Je JH, Margaritondo G (2008) Enhanced x-ray irradiation-induced cancer cell damage by gold nanoparticles treated by a new synthesis method of polyethylene glycol modification. Nanotechnology 19:295104

    Article  Google Scholar 

  28. Wang CH, Liu CJ, Chien CC, Chen HT, Hua TE, Leng WH, Chen HH, Kempson IM, Hwu Y, Hsiao M, Lai TC, Wang JL, Yang CS, Lin HM, Chen YJ, Margaritondo G (2011) X-ray synthesized PEGylated (polyethylene glycol coated) gold nanoparticles in mice strongly accumulate in tumors. Mater Chem Phys 126:352–356

    Article  CAS  Google Scholar 

  29. Cai XQ, Wang CL, Chen HH, Chien CC, Lai SF, Chen YY, Hua TE, Kempson IM, Hwu Y, Yang CS, Margaritondo G (2010) Tailored Au nanorods: optimizing functionality, controlling the aspect ratio and increasing biocompatibility. Nanotechnology 21:335604

    Article  Google Scholar 

  30. Lai SF, Chen WC, Wang CL, Chen HH, Chen ST, Chien CC, Chen YY, Hung WT, Cai X, Li E, Kempson IM, Hwu Y, Yang CS, Tok ES, Tan HR, Lin M, Margaritondo G (2011) One-pot tuning of Au nucleation and growth: from nanoclusters to nanoparticles. Langmuir 27:8424–8429

    Article  CAS  Google Scholar 

  31. Liu CJ, Wang CH, Chen ST, Chen HH, Leng WH, Chien CC, Wang CL, Kempson IM, Hwu Y, Lai TC, Hsiao M, Yang CS, Chen YJ, Margaritondo G (2010) Enhancement of cell radiation sensitivity by pegylated gold nanoparticles. Phys Med Biol 55:931–945

    Article  CAS  Google Scholar 

  32. Hainfeld JF, Slatkin DN, Smilowitz HM (2004) The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:N309–N315

    Article  CAS  Google Scholar 

  33. Goel R, Shah N, Visaria R, Paciotti GF, Bischof JC (2009) Biodistribution of TNF-alpha-coated gold nanoparticles in an in vivo model system. Nanomedicine (London) 4:401–410

    Article  CAS  Google Scholar 

  34. Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53:283–318

    CAS  Google Scholar 

  35. Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102

    Article  CAS  Google Scholar 

  36. Baish JW, Stylianopoulos T, Lanning RM, Kamoun WS, Fukumura D, Munn LL, Jain RK (2011) Scaling rules for diffusive drug delivery in tumor and normal tissues. Proc Natl Acad Sci U S A 108:1799–1803

    Article  CAS  Google Scholar 

  37. Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515

    Article  CAS  Google Scholar 

  38. Alberola AP, Rädler JO (2009) The defined presentation of nanoparticles to cells and their surface controlled uptake. Biomaterials 30:3766–3770

    Article  CAS  Google Scholar 

  39. Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE (2009) Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev 61:428–437

    Article  CAS  Google Scholar 

  40. Todd ME, Tokito MK (1981) Improved ultrastructural detail in tissues fixed with potassium permanganate. Stain Technol 56:335–342

    CAS  Google Scholar 

  41. Sutton JS (1967) Potassium permanganate staining of ultrathin sections for electron microscopy. J Ultrastruct Mol Struct Res 21:424–429

    CAS  Google Scholar 

  42. Wang CH, Chien CC, Yu YL, Liu CJ, Lee CF, Chen CH, Hwu Y, Yang CS, Je JH, Margaritondo G (2007) Structural properties of 'naked' gold nanoparticles formed by synchrotron X-ray irradiation. J Synchrotron Radiat 14:477–482

    Article  CAS  Google Scholar 

  43. Wang CH, Hua TE, Chien CC, Yu YL, Yang TY, Liu CJ, Leng WH, Hwu Y, Yang YC, Kim CC, Je JH, Chen CH, Lin HM, Margaritondo G (2007) Aqueous gold nanosols stabilized by electrostatic protection generated by X-ray irradiation assisted radical reduction. Mater Chem Phys 106:323–329

    Article  CAS  Google Scholar 

  44. Wang CH, Liu CJ, Wang CL, Hua TE, Obliosca JM, Le KH, Hwu Y, Yang CS, Liu RS, Lin HM, Je JH, Margaritondo G (2008) Optimizing the size and surface properties of polyethylene glycol (PEG)-gold nanoparticles by intense x-ray irradiation. J Phys D Appl Phys 41:195301

    Article  Google Scholar 

  45. Metscher BD (2009) MicroCT for comparative morphology: simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues. BMC Physiol 9:11

    Article  Google Scholar 

  46. Chen YT, Lo TN, Chiu CW, Wang JY, Wang CL, Liu CJ, Wu SR, Jeng ST, Yang CC, Shiue J, Chen CH, Hwu Y, Yin GC, Lin HM, Je JH, Margaritondo G (2008) Fabrication of high-aspect-ratio Fresnel zone plates by e-beam lithography and electroplating. J Synchrotron Radiat 15:170–175

    Article  CAS  Google Scholar 

  47. Lo TN, Chen YT, Liu CJ, Chang WD, Lai TY, Wu HJ, Lin IK, Su CI, Shew BY, Je JH, Marganitondo G, Hwu Y (2007) Using e-beam and x-ray lithography techniques to fabricate zone plates for hard x-ray. In: Choi JY, Rah S (eds) Synchrotron Radiation Instrumentation, Pts 1 and 2, vol 879. AIP Conference Proceedings. American Institute of Physics, New York, pp 1466–1469

  48. Chien CC, Tseng PY, Chen HH, Hua TE, Chen ST, Chen YY, Leng WH, Wang CH, Hwu Y, Yin GC, Liang KS, Chen FR, Chu YS, Yeh HI, Yang YC, Yang CS, Zhang GL, Je JH, Margaritondo G (2012) Imaging cells and sub-cellular structures with ultrahigh resolution full-field X-ray microscopy. Biotechnol Adv. doi:10.1016/j.biotechadv.2012.04.005

  49. Cho W-S, Cho M, Jeong J, Choi M, Han BS, Shin H-S, Hong J, Chung BH, Jeong J, Cho M-H (2010) Size-dependent tissue kinetics of PEG-coated gold nanoparticles. Toxicol Appl Pharmacol 245:116–123

    Article  CAS  Google Scholar 

  50. Romberg B, Hennink W, Storm G (2008) Sheddable Coatings for Long-Circulating Nanoparticles. Pharm Res 25:55–71

    Article  CAS  Google Scholar 

  51. Chien CC, Chen HH, Lai SF, Wu KC, Cai X, Hwu Y, Petibois C, Chu YS, Margaritondo G (2012) Gold nanoparticles as high-resolution X-ray imaging contrast agents for the analysis of tumor-related micro-vasculature. J Nanobiotechnology 10:10

    Article  CAS  Google Scholar 

  52. Wu SR, Chen ST, Chu YS, Conley R, Bouet N, Chien CC, Chen HH, Lin CH, Tung HT, Chen YS, Margaritondo G, Je JH, Hwu Y (2012) Nanoresolution radiology of neurons. J Phys D Appl Phys 45:242001

    Google Scholar 

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Authors and Affiliations

  1. Institute of Physics, Academia Sinica, Nankang, Taipei, 115, Taiwan

    C-C. Chien, H. H. Chen & Y. Hwu

  2. Department of Engineering and System Science, National Tsing Hua University, Hsinchu, 300, Taiwan

    C-C. Chien & Y. Hwu

  3. Department of Computer Science, National Chiao Tung University, Hsinchu, 300, Taiwan

    C-C. Cheng & Y-T. Ching

  4. Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, 701, Taiwan

    Y. Hwu

  5. National Synchrotron Light Source-II, Brookhaven National Laboratory, Upton, NY, 11973-5000, USA

    Y. S. Chu

  6. CNRS UMR 5248, CBMN, University of Bordeaux, 33600, Pessac-Cedex, France

    C. Petibois

  7. Division of Experimental Pathology, Tri-Service General Hospital, Taipei, 114, Taiwan

    A. Chen

  8. Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland

    G. Margaritondo

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  1. C-C. Chien
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  2. C-C. Cheng
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  3. H. H. Chen
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  4. Y. Hwu
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  5. Y. S. Chu
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  6. C. Petibois
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  7. A. Chen
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  8. Y-T. Ching
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  9. G. Margaritondo
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Correspondence to Y. Hwu.

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Published in the special paper collection Imaging Techniques with Synchrotron Radiation with guest editor Cyril Petibois.

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Chien, CC., Cheng, CC., Chen, H.H. et al. X-ray microscopy and tomography detect the accumulation of bare and PEG-coated gold nanoparticles in normal and tumor mouse tissues. Anal Bioanal Chem 404, 1287–1296 (2012). https://doi.org/10.1007/s00216-012-6217-y

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  • DOI: https://doi.org/10.1007/s00216-012-6217-y

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