title: Targeting therapy of choroidal neovascularization by use of polypeptide- and PEDF-loaded immunoliposomes under ultrasound exposure.
abstract: Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV). However, the lack of ideal administration route is the biggest bottleneck preventing PEDF from wider clinical use. In this study, we developed a novel PEDF-carrying system which employed immuno-nano-liposomes (INLs) under ultrasound exposure. PEDF-loaded INLs were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and reversely encapsuling PEDF. RF/6A cells were incubated with PEDF-loaded INLs. CNV models of BN rats were injected with PEDF-loaded INLs. MTT assay was used to evaluate the cytotoxicity of the INLs on RF/6A cells. Flow cytometry was conducted to detect the apoptotic rate of cells. Laser scanning confocal microscopy was employed to observe the binding and transmitting process of PEDF-loaded INLs and to calculate the area of CNV in the rat model. The results showed that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal choroidal vessels. The CNV area was significantly decreased in PEDF treatment groups in comparison with control group (P<0.05). Moreover, PEDF-loaded INLs exposed under ultrasound were more efficient in reducing the CNV area (P<0.05). It was concluded that INLs in combination with ultrasonic exposure can transmit PEDF into cytoplasma with high specificity and efficiency, which strengthens the inhibitory effects of PEDF on CNV and reduces its side effects. PEDF-loaded INLs possibly represent a new treatment paradigm for patients with ocular neovascularization.
authors.affiliation: Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. dr_litao@163.com
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005136:Eye Proteins / Q000627:therapeutic use*; D005260:Female; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN; D015843:Serpins / Q000627:therapeutic use*; D014465:Ultrasonics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D008081:Liposomes; D009414:Nerve Growth Factors; D010455:Peptides; D015843:Serpins; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099174:Pigment Epithelium-Derived Factor