화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.23, No.7, 686-695, July, 2015
DOI10.1007/s13233-015-3092-3  Export Citation
Optical imaging, biodistribution and toxicity of orally administered quantum dots loaded heparin-deoxycholic acid
Zehedina Khatun, Md Nurunnabi, Dong Yun Lee1, Youn-Jung Kim2, Youngro Byun3, Kwang Jae Cho4, †, and Yong-kyu Lee†
  • Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungbuk, 380-702, Korea
  • 1Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Korea
  • 2Department of Marine Sciences, Incheon National University, Songdo-dong, Yeonsu-gu, Incheon, 406-840, Korea
  • 3College of Pharmacy, Seoul National University, Seoul, 151-742, Korea
  • 4Department of Otolaryngology, Head & Neck Surgery, The Catholic University of Korea, College of Medicine Uijeongbu St., Mary’s Hospital, Gyeonggi, 480-717, Korea
E-mail:,
Quantum dots (QDs) are considered to be one of the most promising optical imaging probes for biological and biomedical applications. However toxicology is the major concern that limits biological application. Though couple of studies have reported focusing on intravenous administration but, in this study, we have observed toxicity of orally administered QDs for the very first time. QDs were loaded into heparin-conjugated deoxycholic acid (QLHD) conjugates. The orally administered Q-LHD nanoparticles were absorbed through bile acid transporter of small intestine. In vitro genotoxicity was observed by chromosomal aberration and comet assay to learn effect of quantum dot in cell mutation. The amount of cadmium content in different organs was also measured by inductive coupled plasma mass spectroscopy. To observe physiological changes, complete blood count, serum biochemistry and organ histology of Q-LHD treated rats were performed accordingly. The in vivo biodistribution results confirm any acute toxicity or significant variations were noted in the rats. Furthermore, oral administration of the Q-LHD nanoparticles does not cause appreciable toxicity, showing no mentionable histological changes of the organs at 45 days after single dose. Though this current study reveals, potential toxicity of Q-LHD nanoparticles is no longer a limiting factor for extending application of QDs in biomedical imaging but long term in vivo genotoxicity studies further required.
Keywords:quantum dot;nonotoxicology;genotoxicity;serum biochemistry;histology
  1. Kairdolf BA, Smith AM, Stokes TH, Wang MD, Young AN, Nei S, Annu. Rev. Anal. Chem., 6, 143 (2013)
  2. Nurunnabi M, Cho KJ, Choi JS, Huh KM, Lee Y, Biomaterials, 62, 717 (2009)
  3. Kim JS, Cho KJ, Tran TH, Nurunnabi M, Moon TH, Hong SM, Lee YK, J. Colloid Interface Sci., 353(2), 363 (2011)
  4. Fang M, Yuan JP, Peng CW, Pang DW, Li Y, Biomaterials, 34, 8708 (2013)
  5. Tikhomirov G, Hoogland S, Lee PE, Fischer A, Sargent EH, Kelley SO, Nat. Nanotechnol., 6(8), 485 (2011)
  6. Sun LF, Choi JJ, Stachnik D, Bartnik AC, Hyun BR, Malliaras GG, Hanrath T, Wise FW, Nat. Nanotechnol., 7(6), 369 (2012)
  7. Narayanan SS, Sinha SS, Pal SK, J. Phys. Chem., 112, 12716 (2008)
  8. Khatun Z, Nurunnabi M, Cho KJ, Lee Y, ACS Appl. Mater. Interfaces, 4, 3880 (2012)
  9. Khatun Z, Nurunnabi M, Cho KJ, Lee Y, Carbohydr. Polym., 90, 1461 (2012)
  10. Zhang BB, Wang XH, Liu FJ, Cheng YS, Shi DL, Langmuir, 28(48), 16605 (2012)
  11. Qi L, Gao X, ACS Nano, 2, 1403 (2008)
  12. Chen Y, Chen H, Zeng D, Tian Y, Chen F, Feng J, Shi J, ACS Nano, 4, 6001 (2010)
  13. Sigot V, Arndt-Jovin DJ, Jovin TM, Bioconjugate Chem., 21, 1465 (2010)
  14. Medintz IL, Mattoussi H, Clapp AR, Int. J. Nanomedicine., 3, 151 (2008)
  15. Xing Y, Rao J, Cancer Biomark., 4, 307 (2008)
  16. Barroso MM, J. Histochem. Cytochem., 59, 237 (2011)
  17. Albanese A, Tang PS, Chan WCW, Annu. Rev. Biomed. Eng., 14, 1 (2012)
  18. Dong CQ, Irudayaraj J, J. Phys. Chem. B, 116(40), 12125 (2012)
  19. Yang P, Ando M, Taguchi T, Murase N, J. Phys. Chem. C, 114, 20962 (2010)
  20. Janczewski D, Tomczak N, Han MY, Vancso GJ, Macromolecules, 42(6), 1801 (2009)
  21. Wei Y, Jana NR, Tan SJ, Ying JY, Bioconjugate Chem., 20, 1752 (2009)
  22. Liu L, Guo XH, Li Y, Zhong XH, Inorg. Chem., 49(8), 3768 (2010)
  23. Ye L, Yong KT, Liu LW, Roy I, Hu R, Zhu J, Cai HX, Law WC, Liu JW, Wang K, Liu J, Liu YQ, Hu YZ, Zhang XH, Swihart MT, Prasad PN, Nat. Nanotechnol., 7(7), 453 (2012)
  24. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, Bawendi MG, Fragioni JV, Nat. Biotechnol., 25, 1165 (2007)
  25. Law WC, Yong KT, Roy I, Ding H, Hu R, Zhao W, Prasad PN, Small, 5, 1302 (2009)
  26. Yong KT, Law WC, Hu R, Ye L, Liu L, Swihart MT, Prasad PN, Chem. Soc. Rev., 42, 1236 (2013)
  27. Gao J, Chen X, Cheng Z, Curr. Top. Med. Chem., 10, 1147 (2010)
  28. Smith WE, Brownell J, White CC, Afsharinejad Z, Tsai J, Hu X, Polyak SJ, Gao X, Kavanagh TJ, Eaton DL, ACS Nano, 6, 9475 (2012)
  29. Lai L, Lin C, Xiao CQ, Xu ZQ, Han XL, Fu L, Li DW, Mei P, Jiang FL, Guo QL, Liu Y, J. Colloid Interface Sci., 389, 61 (2013)
  30. Peng L, He M, Chen B, Wu Q, Zhang Z, Pang D, Biomaterials, 34, 9545 (2013)
  31. Zheng H, Mortensen LJ, DeLouise LA, J. Biomed. Nanotechnol., 9, 382 (2013)
  32. Aye M, Di GC, Berque-Bestel I, Aime A, Pichon BP, Jammes Y, Barthelemy P, Meo MD, Mutat. Res., 750, 129 (2013)
  33. Aye M, Di GC, MeKaouche M, Steinberg JG, Brerro-Saby C, Barthelemy P, Meo ND, Jammes Y, Mutat. Res., 758, 48 (2013)
  34. Tiwari DK, Jin T, Behari J, Int. J. Nanomedicine, 6, 463 (2011)
  35. Liu Q, Guo B, Rao Z, Zhang B, Gong JR, Nano Lett., 13, 2436 (2013)
  36. Lee DK, Lee YK, Macromol. Res., 18(7), 641 (2010)
  37. Bilbao C, Ferreiro JA, Comendador MA, Sierra LM, Mutat. Res., 503, 11 (2002)
  38. Rjiba-Touati K, Ayed-Boussema I, Guedri Y, Achour A, Bacha H, Abid S, Mutat. Res., 753, 48 (2013)
  39. Nurunnabi M, Khatun Z, Moon WC, Lee G, Lee Y, Quant. Imaging Med. Surg., 2, 219 (2012)
  40. Li L, Nurunnabi M, Nafiujjaman M, Lee Y, Huh KM, J. Control. Release, 171, 241 (2013)
  41. Nurunnabi M, Khatun Z, Nafiujjaman M, Lee DG, Lee Y, ACS Appl. Mater. Interfaces, 5, 8246 (2013)
  42. Nurunnabi M, Khatun Z, Reeck GR, Lee DY, Lee Y, Chem. Commun., 49, 5079 (2013)
  43. Nurunnabi M, Khatun Z, Huh KM, Park SY, Lee DY, Cho KJ, Lee Y, ACS Nano, 7, 6858 (2013)
  44. Khatun Z, Nurunnabi M, Reeck GR, Cho KJ, Lee Y, J. Control. Release, 170, 74 (2013)