title: Investigation on novel chitosan nanoparticle-aptamer complexes targeting TGF-β receptor II.
abstract: In our previous study, a dominant sequence called aptamer S58 antagonized TGF-β-induced myofibroblast transdifferentiation in human Tenon's capsule fibroblasts (HTFs) through sealing the targeting site of TGF-β receptor II (TβR II). However, rapid degradation by ubiquitous nucleases limited the aptamer's efficacy. Chitosan-nanoparticles (CS-NP) are good drug carriers. Herein we synthesises novel chitosan nanoparticle-aptamer S58 complexes called CS(S58)-NP in order to preserve and prolong S58's efficacy. We synthesised CS(S58)-NP at various molar ratios of CS-NP to S58 using an ionic gelation method. Then, the properties of the CS(S58)-NP including particle size, zeta potential, protection capacity, slow-release effect and cytotoxicity were studied. The targeting effect of the CS(S58)-NP was also studied. CS(S58)-NP at molar ratios of 20 and 30 showed high aptamer encapsulation efficiency, powerful aptamer protection, stable sustained-release ability and low cytotoxicity. FITC-labelled CS(S58)-NP could successfully bind to TβR II. As a result, TGF-β-induced cell proliferation and α-SMA expression were both inhibited. Furthermore, the CS(S58)-NP could inhibit TGF-β-induced α-SMA expression for a longer time than naked S58, even in serum. This research applied CS-NP as the aptamer carrier. The research results demonstrate that CS-NP are potentially able to preserve and prolong aptamer S58's efficacy. This study reveals that the use of CS-NP is promising for aptamer delivery and CS(S58)-NP can be a potential anti-scarring therapeutic approach after glaucoma filtration surgery.
authors.affiliation: Department of Ophthalmology, Daping Hospital & Research Institute of Surgery, Third Military Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Guangjun
authors.initials: G
authors.lastname: Xian
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Dawei
authors.initials: D
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry; D002417:Cattle; D002460:Cell Line; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D018125:Receptors, Transforming Growth Factor beta; D048271:Chitosan; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Anti-scarring; Aptamer; Chitosan; Human Tenon's capsule fibroblasts; Nanoparticle; TGF-β