title: Photodynamic efficacy of hypericin targeted by two delivery techniques to hepatocellular carcinoma cells.
abstract: The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry (DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2 cells were analyzed by means of spectrofluorometry and fluorescence microscopy. Spectroscopic measurements demonstrated that Hyp binds to anti-HSA in its monomeric form. The photocytotoxic effect of Hyp depended clearly on the form of Hyp administered, either in free form, loaded into liposomes or conjugated with anti-HSA. While liposomes loaded with Hyp (Lip-Hyp) did not induce significant phototoxicity, both free Hyp or anti-HSA-Hyp inflicted substantial cell mortality, after photoirradiation. The intracellular uptake of Lip-Hyp by HepG2 cells was estimated to be 20% less compared to free Hyp or anti-HSA-Hyp. In spite of the equal uptake of both free Hyp and anti-HSA-Hyp, HepG2 cells demonstrated a relatively higher mortality with anti-HSA-Hyp compared to free Hyp.
authors.affiliation: Pharmaceutical Technology Laboratory, Medical Laser Applications Department, National Institute of Laser Enhanced Sciences (NILES), Cairo University, 12613 Giza, Egypt.
authors.forename: Maha
authors.initials: M
authors.lastname: Fadel
authors.forename: Kawser
authors.initials: K
authors.lastname: Kassab
authors.forename: Tareq
authors.initials: T
authors.lastname: Youssef
mesh_terms: D000873:Anthracenes; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000276:immunology
chemical_list: D000873:Anthracenes; D000911:Antibodies, Monoclonal; D008081:Liposomes; D017319:Photosensitizing Agents; D012709:Serum Albumin; D010569:Perylene; C004965:hypericin
references.citation: Int J Cancer. 2000 Oct 1;88(1):108-14
references.pmid: 10962447
references.citation: J Photochem Photobiol B. 1997 Apr;38(2-3):136-42
references.pmid: 9203374
references.citation: Photochem Photobiol. 1999 Jun;69(6):633-45
references.pmid: 10378001
references.citation: Int J Oncol. 2002 Jan;20(1):181-7
references.pmid: 11743662
references.citation: Int J Oncol. 2007 Mar;30(3):659-67
references.pmid: 17273767
references.citation: BJU Int. 2002 May;89(7):760-3
references.pmid: 11966641
references.citation: Angew Chem Int Ed Engl. 1999 Nov 2;38(21):3116-3136
references.pmid: 10556884
references.citation: J Photochem Photobiol B. 2002 Mar;66(2):89-106
references.pmid: 11897509
references.citation: Cancer Res. 2000 Aug 1;60(15):4200-5
references.pmid: 10945630
references.citation: J Photochem Photobiol B. 1995 Oct;30(2-3):161-9
references.pmid: 8558368
references.citation: Cancer Lett. 2000 Mar 13;150(1):111-7
references.pmid: 10755394
references.citation: Curr Eye Res. 2000 Aug;21(2):597-601
references.pmid: 11148595
references.citation: Biochemistry. 1978 Jun 13;17(12):2464-8
references.pmid: 581060
references.citation: J Natl Cancer Inst. 1993 Mar 17;85(6):443-56
references.pmid: 8445672
references.citation: Photochem Photobiol. 1995 Jul;62(1):199-204
references.pmid: 7638267
references.citation: Transfusion. 1995 May;35(5):392-400
references.pmid: 7740610
references.citation: J Immunol. 1983 Mar;130(3):1473-7
references.pmid: 6185591
references.citation: Photochem Photobiol. 2008 Jan-Feb;84(1):120-7
references.pmid: 18173711
references.citation: Photochem Photobiol. 2009 Jul-Aug;85(4):921-6
references.pmid: 19175752
references.citation: Photochem Photobiol. 1992 Jun;55(6):831-7
references.pmid: 1409890
references.citation: Cancer Res. 2000 Apr 15;60(8):2197-202
references.pmid: 10786684
references.citation: Biochim Biophys Acta. 1992 Jan 23;1115(3):192-200
references.pmid: 1739734
references.citation: Clin Cancer Res. 2005 Feb 15;11(4):1658-68
references.pmid: 15746071
references.citation: Biochim Biophys Acta. 1999 Mar 4;1417(2):211-23
references.pmid: 10082797
references.citation: Br J Cancer. 1986 May;53(5):615-21
references.pmid: 3718819
references.citation: Photochem Photobiol. 2005 Jan-Feb;81(1):183-6
references.pmid: 15250774
references.citation: Proc Natl Acad Sci U S A. 1978 Sep;75(9):4194-8
references.pmid: 279908
references.citation: J Natl Cancer Inst. 2005 Feb 16;97(4):265-72
references.pmid: 15713961
references.citation: J Photochem Photobiol B. 1991 Jun;9(3-4):281-94
references.pmid: 1919873
references.citation: J Surg Res. 2000 Sep;93(1):137-43
references.pmid: 10945955
references.citation: Photochem Photobiol. 1998 Aug;68(2):135-40
references.pmid: 9723207
references.citation: J Photochem Photobiol B. 1992 Jul 30;14(4):383-6
references.pmid: 1403379
references.citation: Lasers Med Sci. 2001;16(4):276-83
references.pmid: 11702633
references.citation: Int J Oncol. 2002 Sep;21(3):531-40
references.pmid: 12168096
references.citation: Cancer Res. 1992 Apr 1;52(7):1916-23
references.pmid: 1348016
references.citation: Photochem Photobiol Sci. 2008 Jul;7(7):844-53
references.pmid: 18597033
references.citation: Nat Rev Drug Discov. 2005 Feb;4(2):145-60
references.pmid: 15688077