title: Combination of targeted PDT and anti-VEGF therapy for rat CNV by RGD-modified liposomal photocyanine and sorafenib.
abstract: OBJECTIVE
  To achieve a combination therapy of targeted PDT and anti-VEGF for choroidal neovascularization (CNV).
  
  
  METHODS
  Arg-Gly-Asp (RGD)-modified liposomes encapsulating photocyanine and sorafenib (RGD-SSL-[P]-[S]) were prepared and characterized. Drug concentration in RGD-SSL-[P]-[S] and irradiation time were optimized on ARPE-19 and HUVEC cells in vitro. A laser-induced CNV rat model was used to assess the efficacy of this targeted combinational system. The effect of RGD-SSL-[P]-[S] on the retinal structure of BN rats was also examined.
  
  
  RESULTS
  The particle size of RGD-SSL-[P]-[S] was approximately 100 nm, with a encapsulation efficiency more than 90% for both photocyanine and sorafenib. From RGD-SSL-[P]-[S], the release rate of photocyanine was approximately 22%, whereas that of sorafeinb was approximately 40% at 48 hours. With the optimal drug concentration and irradiation time, RGD-SSL-[P]-[S] exhibited cytotoxicity only to HUVEC without obvious damage to normal ARPE-19 cells. Rats treated with RGD-SSL-[P]-[S] showed the least CNV area and fluorescein leakage in fluorescein fundus angiography. RGD-SSL-[P]-[S] was also found safe to the rat retina.
  
  
  CONCLUSIONS
  Combination of targeted PDT and anti-VEGF might be an effective therapy for CNV.
authors.affiliation: Peking University Eye Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Jia-lin
authors.initials: JL
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xi
authors.forename: Yu-ling
authors.initials: YL
authors.lastname: Liu
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D008081:Liposomes; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009842:Oligopeptides / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN; D011971:Receptors, Immunologic; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D008081:Liposomes; D009842:Oligopeptides; D010671:Phenylurea Compounds; D017319:Photosensitizing Agents; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; C047981:arginyl-glycyl-aspartic acid; D000077157:Sorafenib
keywords: RGD peptide; anti-VEGF; choroidal neovascularization; liposomes; photocyanine; sorafenib; targeted PDT