title: Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat.
abstract: We evaluated whether specifically and directly targeting human antigen R (HuR), a member of embryonic lethal abnormal vision (ELAV) proteins family, may represent a new potential therapeutic strategy to manage diabetic retinopathy. Nanosystems loaded with siRNA silencing HuR expression (lipoplexes), consisting of solid lipid nanoparticles (SLN) and liposomes (SUV) were prepared. Photon correlation spectroscopy analysis, Zeta potential measurement and atomic force microscopy (AFM) studies were carried out to characterize the complexation of siRNA with the lipid nanocarriers. Nanosystems were evaluated by using AFM and scanning electron microscopy. The lipoplexes were injected into the eye of streptozotocin (STZ)-induced diabetic rats. Retinal HuR and VEGF levels were detected by Western blot and ELISA, respectively. Retinal histology was also carried out. The results demonstrated that retinal HuR and VEGF are significantly increased in STZ-rats and are blunted by HuR siRNA treatment. Lipoplexes with a weak positive surface charge and with a 4:1 N/P (cationic lipid nitrogen to siRNA phosphate) ratio exert a better transfection efficiency, significantly dumping retinal HuR and VEGF levels. In conclusion, we demonstrated that siRNA can be efficiently delivered into the rat retina using lipid-based nanocarriers, and some of the lipoplexes loaded with siRNA silencing HuR expression are potential candidates to manage retinal diseases.
authors.affiliation: Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
authors.forename: Marialaura
authors.initials: M
authors.lastname: Amadio
authors.affiliation: Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pascale
authors.affiliation: NANO-i⿿Research Center on Ocular Nanotechnology, Department of Drug Sciences, University of Catania, Catania, Italy.
authors.forename: Sarha
authors.initials: S
authors.lastname: Cupri
authors.affiliation: NANO-i⿿Research Center on Ocular Nanotechnology, Department of Drug Sciences, University of Catania, Catania, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pignatello
authors.affiliation: Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Osera
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Velia
authors.initials: V
authors.lastname: D Agata
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D Amico
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Leggio
authors.affiliation: Nanomedicine Group, Te.Far.T.I. Center, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruozi
authors.affiliation: Department of Drug Sciences, Section of Pharmacology, University of Pavia, Pavia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy. Electronic address: claudio.bucolo@unict.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bucolo
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D000067780:ELAV-Like Protein 1 / Q000235:genetics* / Q000378:metabolism; D056965:Injections, Intraocular; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008297:Male; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000067780:ELAV-Like Protein 1; C000593998:Elavl1 protein, rat; D008055:Lipids; D008081:Liposomes; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Diabetic retinopathy; HuR/ELAV; Liposomes; Solid lipid nanoparticles; VEGF; siRNA