Investigation on novel chitosan nanoparticle–aptamer complexes targeting TGF-β receptor II

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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.