No abstract

Many synthetic and natural peptides are known to self-assemble to form various nanostructures such as nanofibers, hollow tubes, or ring-like structures. Some of the synthetic peptide molecules are specifically designed to produce well-defined nanostructures by controlling intermolecular interactions. Many environmental conditions such as salt concentration, pH, temperature, and surface characteristics influence intermolecular interactions, hence the process of the self-assembly. Here we studied self-assembly of a genetically engineered protein polymer composed of silk-like and elastin-like repeats on a mica surface. Silk-elastinlike protein polymers (SELPs) consist of tandem repeats of Gly-Ala-Gly-Ala-Gly-Ser from Bombyx mori (silkworm) and Gly-Val-Gly-Val-Pro from mammalian elastin. At a very low polymer concentration of 1 μg/ml, SELPs self-assembled into nanofibrous structures on a mica surface. Examination using atomic force microscopy (AFM) and dynamic light scattering techniques showed that SELPs self-assembled into nanofibers in the presence of the mica surface but not in the bulk state. Ionic strength had a significant influence on nanofiber growth, indicating the importance of electrostatic interactions between the polymer and the mica surface. At low ionic strength, the kinetics of nanofiber growth indicates that the mica surface effectively removed a lag phase by providing nucleating sites, facilitating nanofiber selfassembly of SELPs. Further examination of self-assembly on various surfaces such as silicon, positively charged surface, and hydrophobic surface revealed that negatively charged hydrophilic surface provides optimal surface to facilitate self-assembly of SELPs.

Vector dissemination, transient gene expression and rapid clearance are major obstacles to successful human gene therapy. In this study, we investigated the effect of silk-elastinlike protein polymer (SELP) hydrogels, on biodistribution and anticancer efficacy of adenoviral gene therapy in a head and neck cancer model. Transcriptional activities of adenovirus carrying β-galactosidase (Ad-LacZ) and luciferase (Ad-Luc) reporter genes were evaluated in (nu/nu) mice with head and neck cancer, as a function of polymer concentration. Antitumor efficacy of thymidine kinase encoding adenovirus (Ad-Tk) and ganciclovir (GSV) combination was also evaluated. 4 wt% SELP matrices localized viral release, minimized dissemination to liver and enhanced reporter gene expression levels by 4-8 fold compared to virus alone. SELP-Ad-Tk with GSV reduced tumor volume significantly compared to the virus alone. SELPs provide a means for temporal and spatial control of viral gene delivery to head and neck tumors.