Protein Polymer Technologies Inc.

San Diego, CA, United States

Protein Polymer Technologies Inc.

San Diego, CA, United States

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Greish K.,University of Utah | Frandsen J.,University of Utah | Scharff S.,University of Utah | Scharff S.,University of Marburg | And 5 more authors.
Journal of Gene Medicine | Year: 2010

Background: Adenoviral-directed enzyme prodrug therapy is a promising approach for head and neck cancer gene therapy. The challenges faced by this approach, however, comprise transient gene expression and dissemination of viruses to distant organs. Methods: We used recombinant silk-elastinlike protein polymer (SELP) matrices for intratumoral delivery of adenoviruses containing both thymidine kinase-1 and luciferase genes in a nude mouse model of JHU-022 head and neck tumor. Hydrogels made from two SELP analogues (47K and 815K), with similar silk to elastinlike block ratios but different block lengths, were studied for intratumoral viral delivery. Tumor-bearing mice were followed up for tumor progression and luciferase gene expression concomitantly for 5 weeks. Polymer safety was evaluated through body weight change, blood count, and liver and kidney functions, in addition to gross and microscopic histological examination. Results: SELP-815K analogues efficiently controlled the duration and extent of transfection in tumors for up to 5 weeks with no detectable spread to the liver. An approximately five-fold greater reduction in tumor volume was obtained with matrix-mediated delivery compared to intra-tumoral injection of adenoviruses in saline. SELP matrix proved safe in all injected mice compared to the control group. Conclusions: The SELP-controlled gene delivery approach could potentially improve the anticancer activity of virus-mediated gene therapy at the same time as limiting viral spread to normal organs. Copyright © 2010 John Wiley & Sons, Ltd.


Price D.L.,Sloan Kettering Cancer Center | Price D.L.,Mayo Medical School | Li P.,Sloan Kettering Cancer Center | Li P.,Capital Medical University | And 15 more authors.
Head and Neck | Year: 2016

Background Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. Methods Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. Results GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. Conclusion The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. © 2014 Wiley Periodicals, Inc. Head Neck 38: 237-246, 2016 © 2014 Wiley Periodicals, Inc.


Chang J.,University of Maryland University College | Peng X.-F.,Case Western Reserve University | Hijji K.,University of Maryland University College | Cappello J.,Protein Polymer Technologies Inc. | And 3 more authors.
Journal of the American Chemical Society | Year: 2011

One-dimensional nanostructures are ideal building blocks for functional nanoscale assembly. Peptide-based nanofibers have great potential in building smart hierarchical structures due to their tunable structures at the single residue level and their ability to reconfigure themselves in response to environmental stimuli. We observed that pre-adsorbed silk-elastin-based protein polymers self-assemble into nanofibers through conformational changes on a mica substrate. Furthermore, we demonstrate that the rate of self-assembly was significantly enhanced by applying a nanomechanical stimulus using atomic force microscopy. The orientation of the newly grown nanofibers was mostly perpendicular to the scanning direction, implying that the new fiber assembly was locally activated with directional control. Our method provides a novel way to prepare nanofiber patterned substrates using a bottom-up approach. © 2011 American Chemical Society.


Dinerman A.A.,University of Maryland, Baltimore | Dinerman A.A.,Centocor | Cappello J.,Protein Polymer Technologies Inc. | El-Sayed M.,University of Maryland, Baltimore | And 4 more authors.
Macromolecular Bioscience | Year: 2010

The influence of solute hydrophobicity and charge on partitioning and diffusion in physically crosslinked networks of a genetically engineered SELP polymer was investigated. A series of fluorescent dyes were used to assess the impact of solute charge and hydrophobicity on release behavior. The mechanism of solute release from the SELP hydrogel appeared to vary as a function of dye hydrophobicity. The extent of FITC attachment to amine-terminated G4 dendrimers influenced SELP hydrogel partitioning more than dendrimer diffusion properties. Results suggest the possibility of controlling solute release from SELP hydrogels by modifying the hydrophobicity and surface charge of drugs and drug/polymer conjugates as well as the possibility of "designing-in" solute-specific interactions.Diffusion of small molecular weight compounds and macromolecular probes in silk-elastin-like hydrogels depends on size, charge, and hydrophobicity of the solutes (probes are not depicted in scale). Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gustafson J.A.,University of Utah | Price R.A.,University of Utah | Greish K.,University of Utah | Cappello J.,Protein Polymer Technologies Inc. | Ghandehari H.,University of Utah
Molecular Pharmaceutics | Year: 2010

Recombinant silk-elastin-like protein polymers (SELPs) are well-known for their highly tunable properties on both the molecular and macroscopic hydrogel levels. One specific structure of these polymers, SELP-815K, has been investigated as an injectable controlled delivery system for the treatment of head and neck cancer via a gene-directed enzyme prodrug therapy (GDEPT) approach. Due to its pore size and gelation properties in vivo, SELP restricts the distribution and controls the release of therapeutic viruses for up to one month. It has been shown that SELP-mediated delivery significantly improves therapeutic outcome of the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system in xenograft models of human head and neck cancer. However little is known about potential benefits of this approach with regard to toxicity in the presence of a fully intact immune system. The studies presented here were designed to assess the change in toxicity of the SELP-mediated viral delivery compared to free viral injection in a non-tumor-bearing immune competent mouse model. Toxicity was assessed at 1, 2, 4, and 12 weeks via body weight monitoring, complete blood count (CBC), and blood chemistry. It was found that in the acute and subacute phases (weeks 1-'4) there is significant toxicity in groups combining the virus and the prodrug, and matrix-mediated gene delivery with SELP demonstrates a reduction in toxicity from the 2 week time point through the 4 week time point. At the end of the subchronic phase (12 weeks), signs of toxicity had subsided in both groups. Based on these results, recombinant SELPs offer a significant reduction in toxicity of virus-mediated GDEPT treatment compared to free virus injection in the acute and subacute phases. © 2010 American Chemical Society.


Teng W.,University of Arizona | Huang Y.,University of Arizona | Cappello J.,Protein Polymer Technologies Inc. | Wu X.,University of Arizona
Journal of Physical Chemistry B | Year: 2011

Recombinant protein polymers, evaluated exten-sively as biomaterials for applications in drug delivery and tissue engineering, are rarely reported as being optically transparent. Here we report the notable optical transparency of films composed of a genetically engineered silk-elastinlike protein polymer SELP-47K. SELP-47K films of 100 μm in thickness display a transmittance of 93% in the wavelength range of 350-800 nm. While covalent cross-linking of SELP-47K via glutaraldehyde decreases its transmittance to 77% at the wavelength of 800 nm, noncovalent cross-linking using methanol slightly increases it to 95%. Non- and covalent cross-linking of SELP-47K films also influences their secondary structures and water contents. Cell viability and proliferation analyses further reveal the excellent cytocompatibility of both non- and covalently cross-linked SELP-47K films. The combination of high optical transparency and cytocompatibility of SELP-47K films, together with their previously reported outstanding mechanical properties, suggests that this protein polymer may be useful in unique, new biomedical applications. © 2011 American Chemical Society.


Qiu W.,University of Arizona | Huang Y.,University of Arizona | Teng W.,University of Arizona | Cohn C.M.,University of Arizona | And 2 more authors.
Biomacromolecules | Year: 2010

Due to their improved biocompatibility and specificity over synthetic materials, protein-based biomaterials, either derived from natural sources or genetically engineered, have been widely fabricated into nanofibrous scaffolds for tissue engineering applications. However, their inferior mechanical properties often require the reinforcement of protein-based tissue scaffolds using synthetic polymers. In this study, we report the electrospinning of a completely recombinant silk-elastinlike protein-based tissue scaffold with excellent mechanical properties and biocompatibility. In particular, SELP-47K containing tandemly repeated polypeptide sequences derived from native silk and elastin was electrospun into nanofibrous scaffolds, and stabilized via chemical vapor treatment and mechanical preconditioning. When fully hydrated in 1× - PBS at 37°C, mechanically preconditioned SELP-47K scaffolds displayed elastic moduli of 3.4-13.2 MPa, ultimate tensile strengths of 5.7-13.5 MPa, deformabilities of 100-130% strain, and resilience of 80.6-86.9%, closely matching or exceeding those of protein-synthetic blend polymeric scaffolds. Additionally, SELP-47K nanofibrous scaffolds promoted cell attachment and growth, demonstrating their in vitro biocompatibility. © 2010 American Chemical Society.

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