Journal of Nanoparticle Research

, Volume 13, Issue 1, pp 283–291 | Cite as

Continuous optical coherence tomography monitoring of nanoparticles accumulation in biological tissues

  • M. A. SirotkinaEmail author
  • M. V. Shirmanova
  • M. L. Bugrova
  • V. V. Elagin
  • P. A. Agrba
  • M. Yu. Kirillin
  • V. A. Kamensky
  • E. V. Zagaynova
Research Paper


In this study, dynamics of nanoparticles penetrating and accumulating in biotissue (healthy skin) was investigated in vivo by the noninvasive method of optical coherence tomography (OCT). Gold nanoshells and titanium dioxide nanoparticles were studied. The processes of the nanoparticles penetration and accumulation in biotissue are accompanied by the changes in optical properties of skin which affect the OCT images. The continuous OCT monitoring of the process of the nanoparticles penetration into skin showed that these changes appeared in 30 min after application of nanoparticles on the surface; the time of accumulation of maximal nanoparticles concentration in skin was observed in period of 1.5–3 h after application. Numerical processing of the OCT signal exhibited the increase in contrast between upper and lower parts of dermis and contrast decay of the hair follicle border during 60–150 min. The transmission electron microscopy technique confirmed accumulation of the both types of nanoparticles in biotissue. The novelty of this study is presentation of OCT ability to in vivo monitor dynamics of nanoparticles penetration and their re-distribution within living tissues.


Nanoparticles Continuous OCT monitoring Nanoparticles accumulation In vivo study Nanomedicine Health and safety 



This study was supported in part by the Science and Innovations Federal Russian Agency (projects ## 02.512.11.2244, MD-3018.2009.7), RFBR grants (09-02-97072, 09-02-12215, 09-02-00539, 09-02-97040, 10-02-00744). The authors are grateful to L.B. Snopova (Nizhny Novgorod State Medical Academy) for help in performing the microscopic analysis. Also, the authors thank the Institute of Biochemistry and Physiology of Plants for providing gold–silica nanoshells and the group of companies PROMCHIM (Perm’, Russia) for providing titanium dioxide nanoparticles.


  1. Alvarez-Roma′n R, Naik A, Kalia YN, Guy RH, Fessi H (2004) Skin penetration and distribution of polymeric nanoparticles. J Control Release 99:53–62CrossRefGoogle Scholar
  2. Baroli B (2010) Penetration of nanoparticles and nanomaterials in the skin: fiction or reality? J Pharm Sci 99:21–50CrossRefGoogle Scholar
  3. Borm PJA, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdorster E (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3:11–23CrossRefGoogle Scholar
  4. Cang H, Sun T, Li Z-Y, Chen J, Wiley BJ, Xia Y, Li X (2005) Gold nanocages as contrast agents for spectroscopic optical coherence tomography. Opt Lett 30:3048–3050CrossRefGoogle Scholar
  5. Edlich RF, Winter KL, Lim HW, Cox MJ, Becker DJ, Horovitz JH, Nichter LS, Britt LD, Long WB (2004) Photoprotection by sunscreens with topical antioxidants systemic antioxidants to reduce sun exposure. Long Term Effects Med Implants 14:317–340CrossRefGoogle Scholar
  6. Elder A, Vidyasagar S, DeLouise L (2009) Physicochemical factors that affect metal andmetal oxide nanoparticle passage across epithelial barriers. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(4):434–450Google Scholar
  7. Gelikonov VM, Gelikonov GV, Dolin LS, Kamensky VA, Sergeev AM, Shakhova NM, Gladkova ND, Zagaynova EV (2003) Optical coherence tomography: physical principles and applications. Laser Phys 13:692–702Google Scholar
  8. Gobin AM, Lee MH, Halas NJ, James WD, Drezek RA, West JL (2007) Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer. NanoLetters 7:1929–1934Google Scholar
  9. Innes B, Tsuzuki T, Dawkins H, Dunlop J, Trotter G, Nearn MR, McCormick PG, Edlich F (2002) Nanotechnology and the cosmetic chemist. Cosmet Aerosols Toilet Aust 15:21–24Google Scholar
  10. James WD, Hirsch LR, West JL, O’Neal PD, Payne JD (2007) Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice. J Radioanal Nucl Chem 271:455–459CrossRefGoogle Scholar
  11. Kah JCY, Olivo M, Chow TH, Song KS, Koh KZY, Mhaisalkar S, Sheppard CJR (2009) Control of optical contrast using gold nanoshells for optical coherence tomography imaging of mouse xenograft tumor model in vivo. J Biomed Opt 14:054015CrossRefGoogle Scholar
  12. Khlebtsov NG, Dykman LA (2010) Optical properties and biomedical applications of plasmonic nanoparticles. J Quant Spectrosc Radiat Transf 111:1–35CrossRefGoogle Scholar
  13. Khlebtsov BN, Bogatyrev VA, Dykman LA, Khlebtsov NG (2007) Spectra of resonance light scattering of gold nanoshells: effects of polydispersity and limited electron free path. Opt Spectrosc 102:233–238CrossRefGoogle Scholar
  14. Kim CS, Wilder-Smith P, Ahn Y-C, Liaw L-HL, Chen Z, Kwon YJ (2009) Enhanced detection of early stage oral cancer in vivo by optical coherence tomography using multimodal delivery of gold nanoparticles. J Biomed Opt 14:034008CrossRefGoogle Scholar
  15. Kirillin M, Shirmanova M, Sirotkina M, Bugrova M, Khlebtsov B, Zagaynova E (2009) Contrasting properties of gold nanoshells and titanium dioxide nanoparticles for OCT imaging of skin: Monte Carlo simulations and in vivo study. J Biomed Opt 14:021017-1–021017-11Google Scholar
  16. Lademann J, Weighmann HJ, Schaefer H, Muller G, Sterry W (2000) Investigation of the stability of coated titanium microparticles in a sunscreen. Skin Pharmacol Appl Skin Physiol 13:258–264Google Scholar
  17. Langer R (2004) Transdermal drug delivery: past progress, current status, and future prospects. Adv Drug Deliv Rev 56:557–564CrossRefGoogle Scholar
  18. Lee TM, Oldenburg AL, Sitafalwalla S, Marks DL, Luo W, J-J ToublanF, Suslick KS, Boppart SA (2003) Engineered microsphere contrast agents for optical coherence tomography. Opt Lett 28:1546–1548CrossRefGoogle Scholar
  19. Liu S, Han Y, Yin L, Long L, Liu R (2008) Toxicology studies of a superparamagnetic iron oxide nanoparticle in vivo. Adv Mater Res 47–50:1097–1100CrossRefGoogle Scholar
  20. McNeil LE, Hanuska AR, French RH (2001) Orientation dependence in near-field scattering from TiO2 particles. Appl Opt 40:3726–3736CrossRefGoogle Scholar
  21. Moranti P, Rocco E, Wolf R, Rocco V (2001) Percutaneous absorption and delivery systems. Clin Dermatol 19:489–501CrossRefGoogle Scholar
  22. Parashar UK, Kesherwani V, Saxena PS, Srivastava A (2008) Role of nanomaterials in biotechnology. J Nanomater Biostruct 3:81–87Google Scholar
  23. Park J, Estrada A, Sharp K, Sang K, Schwartz JA, Smith DK, Coleman C, Payne JD, Korgel BA, Dunn AK, Tunnell JW (2008) Two-photon-induced photoluminescence imaging of tumors using near-infrared excited gold nanoshells. Opt Express 16:1590–1599CrossRefGoogle Scholar
  24. Popov AP, MYu Kirillin, Priezzhev AV, Lademann J, Hast J, Myllylä R (2005) Optical sensing of titanium dioxide nanoparticles within horny layer of human skin and their protecting effect against solar UV radiation. Proc SPIE 5702:113–122CrossRefGoogle Scholar
  25. Ryman-Rasmussen J, Riviere J, Monteiro-Riviere N (2006) Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicol Sci 91:159–165CrossRefGoogle Scholar
  26. Teichmann A, Jacobi U, Ossadnik M, Richter H, Koch S, Sterry W, Lademann J (2005) Differential stripping: determination of the amount of topically applied substances penetrated into the hair follicles. J Invest Dermatol 125:264–269Google Scholar
  27. Tinkle SS, Antonini JM, Rich BA, Roberts JR, Salmen R, DePree K, Adkins EJ (2003) Skin as a route of exposure and sensitization in chronic beryllium disease. Environ Health Perspect 111:1202–1208CrossRefGoogle Scholar
  28. Tkachuk LA, Vrublevsky SA, Khlebtsov BN, Melnicov AG, Khlebtsov NG, Zimnykov DA (2005) Optical properties of gold spheroidal particles and nanoshells: effect of the external dielectric medium. Proc SPIE Int Soc Opt Eng 5772:1–10Google Scholar
  29. Toll R, Jacobi U, Richter H, Lademann J, Schaefer H, Blume-Peytavi U (2004) Penetration profile of microspheres in follicular targeting of terminal hair follicles. J Invest Dermatol 123:168–176CrossRefGoogle Scholar
  30. Troutman TS, Barton JK, Romanowski M (2007) Optical coherence tomography with plasmon resonant nanorods of gold. Opt Lett 32:1438–1440CrossRefGoogle Scholar
  31. Zagaynova EV, Shirmanova MV, Orlova AG, Balalaeva IV, Kirillin MYu, Kamensky VA, Bugrova ML, Sirotkina MA (2008a) Gold nanoshells for OCT imaging contrast: from model to in vivo study. In: Proceedings of SPIE 6865 KGoogle Scholar
  32. Zagaynova EV, Shirmanova MV, MYu Kirillin, Khlebtsov BN, Orlova AG, Balalaeva IV, Sirotkina MA, Bugrova ML, Agrba PD, Kamensky VA (2008b) Contrasting properties of gold nanoparticles for optical coherence tomography: phantom, in vivo studies and Monte Carlo simulation. Phys Med Biol 53:4995–5009CrossRefGoogle Scholar
  33. Zaman RT, Diagaradjane P, Wang JC, Schwartz J, Rajaram N, Gill-Sharp KL, Cho SH, Rylander HG, Payne JD, Krishnan S, Tunnell JW (2007) In vivo detection of gold nanoshells in tumors using diffuse optical spectroscopy. IEEE J Sel Topics Quantum Electron 13:1715–1720CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • M. A. Sirotkina
    • 1
    Email author
  • M. V. Shirmanova
    • 1
  • M. L. Bugrova
    • 1
  • V. V. Elagin
    • 1
  • P. A. Agrba
    • 2
  • M. Yu. Kirillin
    • 2
  • V. A. Kamensky
    • 2
  • E. V. Zagaynova
    • 1
  1. 1.Nizhny Novgorod State Medical AcademyNizhny NovgorodRussia
  2. 2.Institute of Applied Physics of RASNizhny NovgorodRussia

Personalised recommendations