title: Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.
abstract: Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.
authors: a Research Institute of Drug Delivery Sciences .|b Faculty of Pharmaceutical Science , and.
authors: Jun
authors: J
authors: Fang
authors: a Research Institute of Drug Delivery Sciences .|b Faculty of Pharmaceutical Science , and.
authors: Kenji
authors: K
authors: Tsukigawa
authors: a Research Institute of Drug Delivery Sciences .|c Department of Applied Microbiology , Sojo University , Kumamoto , Japan.
authors: Long
authors: L
authors: Liao
authors: a Research Institute of Drug Delivery Sciences .
authors: Hongzhuan
authors: H
authors: Yin
authors: b Faculty of Pharmaceutical Science , and.
authors: Kanami
authors: K
authors: Eguchi
authors: a Research Institute of Drug Delivery Sciences .
authors: Hiroshi
authors: H
authors: Maeda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006367:HeLa Cells; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D010778:Photochemotherapy / Q000379:methods; D011137:Polystyrenes / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D012995:Solubility; D020058:Styrene / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D008298:Maleates; D008665:Metalloporphyrins; D008823:Micelles; D011137:Polystyrenes; D011524:Protoporphyrins; C518727:copoly(styrene-maleic acid)-zinc protoporphyrin; C017803:zinc protoporphyrin; D020058:Styrene; C030272:maleic acid; D051547:Heme Oxygenase-1
keywords: Antitumor therapy; EPR effect; styrene-maleic acid copolymer; tumor imaging; tumor targeting; zinc protoporphyrin