Nanoparticles carrying anti-Periostin Antibody enable Specific Targeting of activated Cardiac Fibroblasts

Abstract Cardiac fibrosis after Myocardial Infarction (MI) constitutes the formation of the fibrous scar as part of the wound healing reparative process in the tissue. This scar is essential for replacing the damaged myocardium, and thus preventing the risk of ventricular wall rupture. Nevertheless, scarring may turn excessive by expanding in areas remote to the infarction, causing undesired morphology changes. The increased ventricular stiffness and altered chamber compliance impair cardiac output, and eventually lead to heart failure. Periostin has been marked as a source of interest for its involvement in MI-induced fibrosis. Produced by activated fibroblasts (the scar-forming cells), periostin was found positively correlated with increasing levels of collagen in the myocardium, and upregulated in mouse models of fibrosis-associated-hypertrophic cardiomyopathy. Our study aimed to show that periostin can be used not only as a therapeutic goal itself (for the regulation of post-MI fibrosis), but also as the strategical intermediate to target the activated fibroblasts (prior to inducing therapeutics). Here we show that the conjugation of anti-periostin antibody (AB) to short interfering RNA (siRNA)-based-nanoparticles (NPs) is a feasible and effective practice for this purpose. Produced by the covalent binding of AB to AlgS and the electrostatic interactions between AlgS and siRNA with Ca²⁺, the NPs presented physical features suitable for in-vivo administration. Their capacity to reach cardiac activated fibroblasts in MI-induced mice was governed by the insertion of AB to their surface, enabling to specify gene therapy against periostin to these cells in particular. Importantly, the delivery of NPs with siRNA against periostin resulted in periostin reduction within the infarction, testifying to the potential therapeutic benefit of the targeting NPs, to be further studied.