A phage-targeting strategy for the design of spatiotemporal drug delivery from grafted matrices

Fibrogenesis & Tissue Repair - Tập 4 - Trang 1-16 - 2011
Ritsuko Sawada1,2, Carrie Y Peterson1, Ana Maria Gonzalez3, Bruce M Potenza1, Barbara Mueller4, Raul Coimbra1, Brian P Eliceiri1, Andrew Baird1,3
1Department of Surgery, Division of Trauma, Surgical Critical Care and Burns, University of California San Diego School of Medicine, San Diego, USA
2MabVax Therapeutics, Inc, San Diego, USA
3College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
4Torrey Pines Institute for Molecular Studies, San Diego, USA

Tóm tắt

The natural response to injury is dynamic and normally consists of complex temporal and spatial cellular changes in gene expression, which, when acting in synchrony, result in patent tissue repair and, in some instances, regeneration. However, current therapeutic regiments are static and most rely on matrices, gels and engineered skin tissue. Accordingly, there is a need to design next-generation grafting materials to enable biotherapeutic spatiotemporal targeting from clinically approved matrices. To this end, rather then focus on developing completely new grafting materials, we investigated whether phage display could be deployed onto clinically approved synthetic grafts to identify peptide motifs capable of linking pharmaceutical drugs with differential affinities and eventually, control drug delivery from matrices over both space and time. To test this hypothesis, we biopanned combinatorial peptide libraries onto different formulations of a wound-healing matrix (Integra®) and eluted the bound peptides with 1) high salt, 2) collagen and glycosaminoglycan or 3) low pH. After three to six rounds of biopanning, phage recovery and phage amplification of the bound particles, any phage that had acquired a capacity to bind the matrix was sequenced. In this first report, we identify distinct classes of matrix-binding peptides which elute differently from the screened matrix and demonstrate that they can be applied in a spatially relevant manner. We suggest that further applications of these combinatorial techniques to wound-healing matrices may offer a new way to improve the performance of clinically approved matrices so as to introduce temporal and spatial control over drug delivery.

Tài liệu tham khảo

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