This Phase I proposal addresses the significant need for improved treatment options for patients with liver cancer, the fifth highest incidence of cance in the world. Because of the lack of symptoms, hepatocellular carcinoma (HCC) is detected at advanced stages in 84% of cases, for which the 1-year survival rate is 22% and at 5 years it is 5%. The only curative option for advanced HCC is surgical liver resection and liver transplantation, unfortunately not available to most patients due to the lack of donor livers and the rapid progression of the disease. As HCC is generally unresponsive to systemic chemotherapy, transcatheter arterial chemoemobolization (TACE) is the most widely used, localized treatment that can slow the progression of the disease. Current embolizing agents are deficient in precision of catheter delivery or compatibility for effective delivery of chemotherapeutic agents, especially high-molecular weight biotherapeutics. The objective of the proposed work is to develop a novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk- elastinlike protein), which based on our previous work has demonstrated properties uniquely suited for this application. Unlike existing agents, the SELP embolizing agent would be injectable as a liquid, able to penetrate into the tumor arteries, and transform to an insoluble hydrogel in-situ forming a substantially durable occlusion. The embolizing liquid would be completely aqueous and compatible with drugs and new biotherapeutics, enabling their localized controlled release. The protein-based SELP would eventually biodegrade, enabling subsequent TACE treatments. If successful, SELP liquid embolic would enable the controlled delivery of chemotherapeutic drugs and new biotherapeutic agents with increased precision of transcatheter delivery for more selective embolization, reduced off-target toxicity, and reduced collateral damage to the healthy liver. Consequently, TACE treatment could be offered to a larger patient population with greater number of tumors and/or greater tumor size.
The aims of the research are: (1) to develop SELP liquid embolic injection solution formulations;(2) to determine the gelation rate and gel strength of SELP fluids at their maximum injectable viscosity;(3) to assess their occlusion of simulated arterial channels in-vitro using a microfluidic device;and (4) evaluate the performance of SELP fluids in transcatheter arterial embolization in-vivo in the liver.
This Phase I proposal details the rationale and the research plan for the development of a novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk- elastinlike protein), for treatment of unresectable hepatocellular carcinoma by transcatheter arterial chemoembolization (TACE). The SELP embolic would improve the precision of embolization, the compatibility with newly developed drugs, and the selectivity of tumor-specific therapy. Consequently, TACE treatment could be offered to a larger patient population with greater number of tumors and/or greater tumor size, for which few treatment options exist.
|Poursaid, Azadeh; Jensen, Mark Martin; Huo, Eugene et al. (2016) Polymeric materials for embolic and chemoembolic applications. J Control Release :|
|Poursaid, Azadeh; Price, Robert; Tiede, Andrea et al. (2015) In situ gelling silk-elastinlike protein polymer for transarterial chemoembolization. Biomaterials 57:142-52|