화학공학소재연구정보센터
Macromolecular Research, Vol.19, No.5, 487-494, May, 2011
Heparin-Based Self-Assembled Nanoparticles for Photodynamic Therapy
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Novel heparin-based self-assembled nanoparticles were developed for photodynamic cancer therapy. A heparin-poly(β-benzyl-L-aspartate) (HP) amphiphilic copolymer was synthesized for effective delivery of a hydrophobic photosensitizer, pheophorbide a (Pheo). The anti-coagulant activity of the HP copolymer decreased significantly, as measured by an anti-FXa chromogenic assay. Pheo was effectively incorporated into the HP nanoparticles using a dialysis technique. A good drug-loading content was obtained by altering the composition of the HP copolymer and Pheo/HP feed ratio. The Pheo-loaded HP nanoparticles had an average diameter of 117-189 nm, a negatively charged surface, and a sustained drug release pattern. These properties may allow them to passively target the tumor site through an enhanced permeability and retention (EPR) effect. Furthermore, the Pheo-loaded HP nanoparticles demonstrated marked photocytotoxicity and minimal darktoxic without a light treatment. The 6HP-Pheo15 nanoparticles were internalized into SCC7 cancer cells and damaged the cells after a light treatment. This suggests that HP nanoparticles have potential as an effective delivery system for clinical PDT.
  1. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q, J. Natl. Cancer Inst., 90, 889 (1998)
  2. Macdonald IJ, Dougherty TJ, J. Porphyrins Phthalocyanine, 5, 105 (2001)
  3. Dolmans DE, Fukumura D, Jain RK, Nat. Rev. Cancer, 3, 380 (2003)
  4. Fingar VH, J. Clin. Laser Med. Surg., 14, 323 (1996)
  5. Fingar VH, Kik PK, Haydon PS, Cerrito PB, Tseng M, Abang E, Wieman TJ, Br. J. Cancer, 79, 1702 (1999)
  6. Castano AP, Mroz P, Hamblin MR, Nat. Rev. Cancer, 6, 535 (2006)
  7. Gollnick SO, Owczarczak B, Maier P, Lasers Surg. Med., 38, 509 (2006)
  8. Oleinick NL, Evans HH, Radiat. Res., 150, S146 (1998)
  9. Vrouenraets MB, Visser GWM, Snow GB, van Dongen GAMS, Anticancer Res., 23, 502 (2003)
  10. Castano AP, Demidova TN, Hamblin MR, Photodiagn. Photodyn. Ther., 2, 91 (2005)
  11. Detty MR, Gibson SL, Wagner SJ, J. Med. Chem., 47, 3897 (2004)
  12. Richter AM, Waterfield E, Jain AK, Canaan JA, Allison BA, Levy JG, Photochem. Photobiol., 57, 1000 (1993)
  13. Damoiseau X, Schuitmaker HJ, Lagerberg JWM, Hoebeke M, J. Photochem. Photobiol. B-Biol., 60, 50 (2001)
  14. Li F, Bae B, Na K, Bioconjugate Chem., 21, 1312 (2010)
  15. Bae B, Na K, Biomaterials, 31, 6325 (2010)
  16. Rossi LM, Silva PR, Vono LLR, Fernandes AU, Tada DB, Baptista MS, Langmuir, 24(21), 12534 (2008)
  17. Bechet D, Couleaud P, Frochot C, Viriot ML, Guillemin F, Barberi-Heyob M, Trends Biotechnol., 26, 612 (2008)
  18. Rijcken CJF, Hofman JW, van Zeeland F, Hennink WE, van Nostrum CF, J. Control. Release, 124, 144 (2007)
  19. Li B, Moriyama EH, Li F, Jarvi MT, Allen C, Wilson BC, Photochem. Photobiol., 83, 1505 (2007)
  20. Knop K, Mingotaud AF, El-Akra N, Violleau F, Souchard JP, Photochem. Photobiol., 8, 396 (2009)
  21. Jones MC, Leroux JC, Eur. J. Pharm. Biopharm., 48, 101 (1999)
  22. van Nostrum CF, Adv. Drug Deliv. Rev., 56, 9 (2004)
  23. Torchilin VP, Pharm. Res., 24, 1 (2007)
  24. Ferrario A, von Tiehl KF, Rucker N, Schwarz MA, Gill PS, Gomer CJ, Cancer Res., 60, 4066 (2000)
  25. Linhardt RJ, Chem. Ind., 2, 45 (1991)
  26. Linhardt RJ, J. Med. Chem., 46, 2551 (2003)
  27. Mousa SA, Petersen LJ, Thromb. Haemostasis, 102, 258 (2009)
  28. Bobek V, Kovarik J, J. Biomed. Pharmacother., 58, 213 (2004)
  29. Niers TM, Klerk CP, Dinisio M, van Noorden CJ, Buller HR, Reitsma PH, Richel DJ, Crit. Rev. Oncol. Hematol., 61, 195 (2007)
  30. Smorenburg SM, van Noorden CJ, Pharmacol. Rev., 53, 93 (2001)
  31. Park KS, Lee CY, Kim YS, Yu M, Park RW, Kim IS, Kim SY, Byun Y, J. Control. Release, 114, 300 (2006)
  32. Cho KJ, Moon HT, Park G, Jeon OC, Byun Y, Lee YK, Bioconjugate Chem., 19, 1346 (2008)
  33. Thorpe PE, Derbyshire EJ, Andrade SP, Press N, Knowles PP, King S, Watson GJ, Yang YC, Bette MR, Cancer Res., 53, 3000 (1993)
  34. Lee GY, Kim SK, Byun Y, J. Control. Release, 123, 46 (2007)
  35. Li L, Huh KM, Lee YK, Kim SY, Macromol. Res., 18, 153 (2009)
  36. Fernandez JM, Bilgin MD, Grossweiner LI, J. Photochem. Photobiol. B-Biol., 37, 131 (1997)
  37. ROder B, Hanke T, Oelckers S, Hackbarth S, Symietz C, J. Porphyrins Phthalocyanines, 4, 37 (2000)
  38. Hajri A, Wack S, Meyer C, Smith MK, Leberquier C, Kedinger M, Aprahamian M, Photochem. Photobiol., 75, 140 (2002)
  39. Tang PM, Liu XZ, Zhang DM, Fong WP, Fung KP, Cancer Biol. Ther., 8, 533 (2009)
  40. Tomita A, Kajiura T, Kimura S, Trace Nutr. Res., 26, 88 (2009)
  41. Capila I, Linhardt RJ, Angew. Chem.-Int. Edit., 41, 390 (2002)
  42. Casu B, Vlodavsky I, Sanderson RD, Pathophysiol. Haemostasis Thromb., 36, 195 (2008)
  43. Barzu T, van Rijn JLML, Petitou M, Molho P, Tobelem G, Caen JP, Biochem. J., 238, 847 (1986)
  44. Bisio A, Vecchietti D, Citterio L, Guerrini M, Raman R, Bertini S, Eisele G, Naggi A, Sasisekharan R, Torri G, Thromb. Haemostasis, 102, 865 (2009)
  45. Nowakowska M, Zapotoczny S, Sterzel M, Polym. Int., 56, 635 (2007)
  46. Duncan R, Sat YN, Ann. Oncol., 9, 39 (1998)
  47. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K, J. Control. Release, 65, 271 (2000)
  48. Konan YN, Gurny R, Allemann E, J. Photochem. Photobiol. B-Biol., 66, 89 (2002)
  49. Detty MR, Gibson SL, Wagner SJ, J. Med. Chem., 47, 3897 (2004)