Abstract 2888: Sensitization of radiation resistant colon cancer - The oxygenated microbubble hydrogel approach

Abstract

Abstract Background: Hypoxia, a state of reduced oxygen that develops within the tumor due to its irregular vasculature, could result in treatment resistance. Mounting evidence suggests that reoxygenation of the tumor could improve outcomes of conventional cancer therapies. Our approach combats hypoxia using oxygenated lipid microbubbles (OMB) loaded in a temperature sensitive gel. The OMB would carry the oxygen while the gel would sustain its release into the tumor microenvironment. Objectives: To formulate an oxygen loaded MB dispersed in a temperature sensitive poloxamer hydrogel for intratumoral administration. Methods: OMB were generated by first preparing a liposomal mixture DSPC:DSPE-PEG2000, which was dispersed in a thermosensitive poloxamer hydrogel (P407:P188). This was pressurized with oxygen and vortexed in a gas-tight vial. Characterizations included OMB size distribution, injectability, thermosensitivity, oxygen loading and release, and the impact of the formulation on efficacy of radiotherapy against a colon cancer cell line (HCT116) was evaluated. Results: DSPC:DSPE-PEG2000 liposomes at a molar ratio of 94:6 dispersed in P407:P188 (21:6.5 %w/w) generated OMB with a size distribution in the acceptable range of 0.8-8 µm. Formulations were within the established limits of injectability (F<38N) at room temperature, and gelled near physiological temperatures enabling a sustained release of oxygen.. The formulation co-treatment enhanced radiotherapy significantly as evidenced by the remarkable reductions of clonogenic survival rates in both hypoxic and normoxic HCT116 cells (reduction by 78% vs 68% compared to just their respective radiated controls; p<0.0001 for both cases). Conclusion: Reoxygenation with a newly developed OMB hydrogel formulation effectively sensitized HCT116 to radiotherapy in vitro. Studies are underway to explore the importance of reoxygenation rate and extent for optimal tumor sensitization. Citation Format: Ashok David Jose, Celine Hui-Ning Chong, Jagdish Jaiswal, Zimei Wu, Sachin Sunil Thakur. Sensitization of radiation resistant colon cancer - The oxygenated microbubble hydrogel approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2888.