Development of photodynamic and RNA medicine combination therapies for pancreatic ductal adenocarcinoma

Vida Karimnia; Frank Slack; Jonathan Celli

doi:10.1117/12.2650744

14 March 2023 Development of photodynamic and RNA medicine combination therapies for pancreatic ductal adenocarcinoma

Vida Karimnia, Frank Slack, Jonathan Celli

Proceedings Volume 12359, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI; 1235902 (2023) https://doi.org/10.1117/12.2650744
Event: SPIE BiOS, 2023, San Francisco, California, United States

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal of human malignancies. The failure of myriad trials evaluating chemotherapy and/or targeted agent combinations to produce substantial gains in survival continues to motivate the investigation of new therapeutic strategies. Recent studies have demonstrated exciting potential of RNA medicine approaches to therapeutically target microRNAs (miRNA, small non-coding RNAs) which have been shown to regulate PDAC growth, survival and chemoresistance. However, while various miRNA therapies have been discussed for the past decade, challenges with delivery to most disease tissues have restricted their therapeutic use to liver and kidney disease. Here we explore the combination with photodynamic therapy (PDT) to enhance delivery of nanoparticles carrying RNA medicine agents through fibrotic PDAC stroma, and mechanistically synergize with depletion or enrichment of target miRNAs. Using transfection of miRNA mimics and inhibitors in PDAC cells we have evaluated a small panel of miRNAs that could serve as promising targets for either depletion or enrichment. In cell culture studies we find that PDT using verteporfin can enhance RNA medicine efficacy both through depletion of PDAC stroma (previously reported) to significantly enhance delivery to target tissue, and by synergizing mechanistically at the molecular level. In ongoing studies we are now examining the most promising combinations in murine xenografts. Taken together with clinical studies by others establishing the feasibility of PDT for PDAC these results indicate further promise of leveraging PDT to synergistically enhance emerging RNA medicine approaches.

Conference Presentation

Citation Download Citation

Vida Karimnia, Frank Slack, and Jonathan Celli "Development of photodynamic and RNA medicine combination therapies for pancreatic ductal adenocarcinoma", Proc. SPIE 12359, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI, 1235902 (14 March 2023); https://doi.org/10.1117/12.2650744

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