(0700) Polymer Delivery System for Radiosensitizing Agents: A Pilot Murine Study

Introduction: Off-target effects of systemically administered therapies have been a major hurdle in designing therapies with desired efficacy and acceptable toxicity. The ability to decrease mortality and improve survival for patients with head & neck squamous cell carcinoma (HNSCC) has been a longstanding goal. We have developed a modular polymer sheet that is: biocompatible, slowly degradable, radiopaque, can serve as a platform to deliver chemotherapeutic agents, and contains unique gold nanostars (GNS) that can mitigate the dose of required radiation therapy and modulate drug release kinetics. This polymer wrap is designed to be applied intraoperatively to the surgical bed after removing or debulking the tumor, thus allowing for enhanced postoperative radiotherapy, and also functioning as a platform for therapeutic agent delivery. Herein we describe pre-clinical data in a mouse model.

Methods: Mice underwent flank injections with SCC7 (mouse HNSCC), then surgical debulking when tumor volume reached 1cm3 in size, and polymer placement with either cisplatin (4x2Gy) or cisplatin + GNS (4x2Gy). Other mouse groups included full-dose radiation without polymer (4x4Gy) or no treatment (0Gy). Fractionated radiation was administered, and tumor growth measured daily.

Results: At day 25, mice who underwent placement of polymer with cisplatin + GNS experienced a 71% reduction in tumor volume compared to full dose radiation alone (621 mm3 vs 2120 mm3). Mice with cisplatin polymer experienced a 61% reduction in tumor volume compared to full dose radiation alone (832 mm3 vs 2120 mm3). There was a 26% reduction in tumor volume among polymer with cisplatin + GNS vs. cisplatin polymer.

Conclusions: Application of a polymer impregnated with radiosensitizing agents cisplatin +/- GNS in a murine HNSCC model demonstrated >50% reduction in tumor volume. This technique achieved superior tumor control compared to radiotherapy alone, with half the radiation dosage. Use of this polymer delivery system should be further studied for potential clinical use in humans as this could have great impact on the outcomes and quality of life for our patients.