Cathepsin K-targeted sub-micron particles for regenerative repair of vascular elastic matrix.

Abstract

Proactive screening of high risk elderly patients now enables early detection of Abdominal Aortic Aneurysms (AAAs). Current management of small, growing AAAs is limited to passive, imaging based growth monitoring. There are also no established drug-based therapeutic alternatives to surgery for AAAs, which is unsuitable for many elderly patients, and none which can achieve restore disrupted and lost elastic matrix in the AAA wall, which is essential to achieve growth arrest or regression. We seek to test the feasibility of a regenerative therapy based on localized, one time delivery of drug-releasing Sub-Micron-sized drug delivery polymer Particles (SMPs) that are also uniquely chemically functionalized on their surface to also provide them pro-elastin-regenerative & anti-matrix degradative properties, and also conjugated with antibodies targeting cathepsin K, an elastolytic enzyme that is highly overexpressed in AAA tissues; the latter serves as a modality to enable targeted binding of the SMPs to the AAA wall following intravenous infusion, or intraoartal, catheter-based delivery. Such SMPs can potentially stimulate structural repair in the AAA wall following one time infusion to delay or prevent AAA growth to rupture. The therapy can provide a non-surgical treatment option for high risk AAA patients.