화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.85, 66-74, May, 2020
DOI10.1016/j.jiec.2020.01.018  Export Citation
Photothermally enhanced photodynamic therapy based on glutathione-responsive pheophorbide a-conjugated gold nanorod formulations for cancer theranostic applications
Jongseon Choi1, and So Yeon Kim1, 2, †
  • 1Graduate School of Energy Science and Technology, Chungnam National University, Daejeon 34134, Republic of Korea
  • 2Department of Chemical Engineering Education, College of Education, Chungnam National University, Daejeon 34134, Republic of Korea
E-mail:
Nanocarriers have provided a new platform for the selective delivery of therapeutic agents into targeted cells and tissues using safe, efficient, and tractable routes. In particular, the integration of multiple therapeutic/diagnostic modalities into a single system has the great potential of enhancing theranostic efficiency against serious diseases with reduced side effects. In this study, a new light-triggered theranostic system using photosensitizer-conjugated gold nanorods (AuNR) with glutathione (GSH)- sensitive linkages was developed for cancer imaging and combinational phototherapy of photodynamic therapy (PDT) and photothermal therapy (PTT) to achieve a synergistic cancer treatment. AuNRs with various aspect ratios were prepared as photothermal agents, and then a folic acid (FA)-PEG block copolymer (FAP) and pheophorbide a (Pheo) were chemically conjugated to the surface of AuNRs for active tumor targeting and PDT, respectively. The configuration of Pheo-conjugated AuNR nanocarriers has been precisely controlled through adjusting the feed composition ratio and the relationship between aspect ratio and absorption band of AuNRs. In particular, an AuNR with an aspect ratio of 3.84 and longitudinal plasmon resonance at 873 nm (Pheo-conjugated AuNR100) exhibited superior performance in singlet oxygen generation, photothermal conversion effect, and GSH-mediated selective release of Pheo. Moreover, it also showed tumor targeting activity and a PDT-PTT synergistic effect. These results indicate that this multifunctional AuNR system with tumor targeting ability and GSH-sensitive linkages would be highly efficient for noninvasive cancer treatment by integrating cancer imaging diagnostics and synergistic therapy.
Keywords:Photothermal therapy Gold nanorod Photodynamic therapy Drug delivery Targeting
  1. Castano AP, Mroz P, Hamblin MR, Nat. Rev. Cancer, 6, 535 (2006)
  2. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q, J. Natl. Cancer Inst., 90, 889 (1998)
  3. Ackroyd R, Kelty C, Brown N, Reed MJP, Photochem. Photobiol., 74, 656 (2001)
  4. Dolmans DE, Fukumura D, Jain RK, Nat. Rev. Cancer, 3, 380 (2003)
  5. Mroz P, Huang YY, Hamblin MR, Biophotonics Immune Responses V, 7565, 756503 (2010)
  6. Wilson BC, Can. J. Gastroenterol., 16, 393 (2002)
  7. Konan YN, Gurny R, Allemann E, J. Phtochem. Photobiol. B Biol., 66, 89 (2002)
  8. Yasuda K, Ganguly S, Schuetz EG, J. Drug Metab. Dispos., 46, 1725 (2018)
  9. ROder B, Hanke T, Oelckers S, Hackbarth S, Symietz C, J. Porphyrins Phthalocyanines, 4, 37 (2000)
  10. Chen WR, Adams RL, Higgins AK, Bartels KE, Nordquist RE, Cancer Lett., 98, 169 (1996)
  11. Choi J, Yang J, Jang E, Suh JS, Huh YM, Lee K, Haam S, Anticancer Agents Med. Chem., 11, 953 (2011)
  12. Huang X, El-Sayed IH, El-Sayed MA, Methods Mol. Biol., 343 (2010).
  13. Loo C, Lowery A, Halas N, West J, Drezek R, Nano Lett., 5, 709 (2005)
  14. Morton JG, Day ES, Halas NJ, West JL, Methods Mol. Biol., 624, 101 (2010)
  15. Chen CL, Kuo LR, Chang CL, Hwu YK, Huang CK, Lee SY, Chen K, Lin SJ, Huang JD, Chen YY, Biomaterials, 31, 4104 (2010)
  16. Choi WI, Kim JY, Kang C, Byeon CC, Kim YH, Tae G, ACS Nano, 5, 1995 (2011)
  17. Dickerson EB, Dreaden EC, Huang X, El-Sayed IH, Chu H, Pushpanketh S, McDonald JF, El-Sayed MA, Cancer Lett., 269, 57 (2008)
  18. El-Sayed IH, Huang X, El-Sayed MA, Cancer Lett., 239, 129 (2006)
  19. Huang X, Jain PK, El-Sayed IH, El-Sayed MA, Lasers Med. Sci., 23, 217 (2008)
  20. Kennedy LC, Bickford LR, Lewinski NA, Coughlin AJ, Hu Y, Day ES, West JL, Drezek RA, Small, 7, 169 (2011)
  21. Lin KY, Bagley AF, Zhang AY, Karl DL, Yoon SS, Batia SN, J. Nano Life, 1, 277 (2010)
  22. von Maltzahn G, Park JH, Agrawal A, Bandaru NK, Das SK, Sailor MJ, Bhatia SN, Cancer Res., 69, 3892 (2009)
  23. Huang XH, El-Sayed IH, Qian W, El-Sayed MA, J. Am. Chem. Soc., 128(6), 2115 (2006)
  24. Lohse SE, Murphy CJ, Chem. Mater., 25, 1250 (2013)
  25. Ma H, Bendix PM, Oddershede LB, Nano Lett., 12, 3954 (2012)
  26. Nikoobakht B, El-Sayed MA, Chem. Mater., 15, 1957 (2003)
  27. Nepal D, Park K, Vaia RA, Small, 8, 1013 (2012)
  28. Vigderman L, Khanal BP, Zubarev ER, Adv. Mater., 24(36), 4811 (2012)
  29. Cong B, Kan C, Wang H, Liu J, Xu H, Ke S, J. Mater. Sci. Chem. Eng., 2, 20 (2014)
  30. Gormley AJ, Larson N, Banisadr A, Robinson R, Frazier N, Ray A, Ghandehari H, J. Control. Release, 166, 130 (2013)
  31. Jang BS, Park JY, Tung CH, Kim IH, Choi Y, ACS Nano, 5, 1086 (2011)
  32. Young JK, Figueroa ER, Drezek RA, Ann. Biomed. Eng., 40, 438 (2012)
  33. Guillemard V, Saragovi HU, Cancer Res., 61, 694 (2001)
  34. Sun Y, Chen Z, Yang X, Huang P, Zhou X, Du X, Nanotechnology, 20, 135102 (2009)
  35. Castellanos MM, Colina CM, J. Phys. Chem. B, 117(40), 11895 (2013)
  36. Lewis DJ, Glover PB, Solomons MC, Pikramenou Z, J. Am. Chem. Soc., 133, 1033 (2010)
  37. Yang D, Chen WL, Hu JH, J. Phys. Chem. B, 118(43), 12311 (2014)
  38. Hong R, Han G, Fernandez JM, Kim BJ, Forbes NS, Rotello VM, J. Am. Chem. Soc., 128(4), 1078 (2006)
  39. Saito G, Swanson JA, Lee KD, Adv. Drug Deliv. Rev., 55, 199 (2003)
  40. Schafer FQ, Buettner GR, Free Radical Biol. Med., 30, 1191 (2001)
  41. Elnakat H, Ratnam M, Adv. Drug Deliv. Rev., 56, 1067 (2004)
  42. Geszke M, Murias M, Balan L, Medjandi G, Korczynski J, Moritz M, Lulek J, Schneider R, Acta Biomater., 7, 1327 (2011)
  43. Shmeeda H, Mak L, Tzemach D, Astrahan P, Tarshish M, Gabizon A, Mol. Cancer Ther., 5, 818 (2006)
  44. Bharathiraja S, Manivasagan P, Moorthy MS, Bui NQ, Jang B, Phan TTV, Jung WK, Kim YM, Lee KD, Oh J, Eur. J. Pharm. Biopharm., 123, 20 (2018)
  45. Liu L, Xie HJ, Mu LM, Liu R, Su ZB, Cui YN, Xie Y, Lu WL, Int. J. Nanomed., 13, 8119 (2018)
  46. Xin J, Wang S, Wang B, Wang J, Wang J, Zhang L, Xin B, Shen L, Zhang Z, Yao C, Int. J. Nanomed., 13, 2017 (2018)
  47. Lee J, Lee YH, Jeong CB, Choi JS, Chang KS, Yoon M, J. Nanobiotechnol., 16, 104 (2018)
  48. Chien YH, Chou YL, Wang SW, Hung ST, Liau MC, Chao YJ, Su CH, Yeh CS, ACS Nano, 7, 8516 (2013)
  49. Li K, Jiang YH, Ding D, Zhang XH, Liu YT, Hua JL, FengSS, Liu B, Chem. Commun., 47, 7323 (2011)
  50. Meier R, Henning TD, Boddington S, Tavri S, Arora S, Piontek G, Rudelius M, Corot C, Daldrup-Link HE, Radiology, 255, 527 (2010)
  51. Zhang D, Wu M, Zeng YY, Wu LJ, Wang QT, Han X, Liu XL, Liu JF, ACS Appl. Mater. Interfaces, 7, 8176 (2015)
  52. Sau TK, Murphy CJ, Langmuir, 20(15), 6414 (2004)
  53. Zhao L, Kim TH, Ahn JC, Kim HW, Kim SY, J. Mater. Chem. B, 1, 5806 (2013)
  54. Frens G, Nature, 241, 20 (1973)
  55. Choi J, Lee SE, Park JS, Kim SY, Biotechnol. Bioeng., 115(5), 1340 (2018)
  56. Hu M, Chen JY, Li ZY, Au L, Hartland GV, Li XD, Marquez M, Xia YN, Chem. Soc. Rev., 35, 1084 (2006)
  57. Hinde E, Thammasiraphop K, Duong HTT, Yeow J, Karagoz B, Boyer C, Gooding JJ, Gaus K, Nat. Nanotechnol., 12(1), 81 (2017)
  58. Zhou ZX, Ma XP, Jin EL, Tang JB, Sui MH, Shen YQ, Van Kirk EA, Murdoch WJ, Radosz M, Biomaterials, 34, 5722 (2013)
  59. He CB, Hu YP, Yin LC, Tang C, Yin CH, Biomaterials, 31, 3657 (2010)
  60. Loukanov A, Emin S, Microsc. Res. Tech., 79, 799 (2016)
  61. Yang C, Gao S, Kjems J, J. Mater. Chem. B, 2, 8608 (2014)
  62. Miranda N, Gerola AP, Novello CR, Ueda-Nakamura T, de Oliveira Silva S, et al., Photodiagn. Photodyn. Ther., 19, 256 (2017)
  63. Bonechi C, Donati A, Lampariello R, Martini S, Picchi M, Ricci M, Rossi C, Spectroc. Acta Pt. A-Molec. Biomolec. Spectr., 60, 1411 (2004)
  64. Jin H, Nam J, Park J, Jung S, Im K, Hur J, Park JJ, Kim JM, Kim S, Chem. Commun., 47, 1758 (2011)
  65. Li H, Niu Y, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 89, 160 (2018)
  66. Kumar P, Agnihotri S, Roy I, J. Nanomed. Nanotechnol., 7, 392 (2016)