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Nanomedicine and Nanoscale Delivery (Focus Group – NND)

Targeted Delivery of Apoptotic Priming Agents to PDAC to Overcome TME Nutrient-Driven Chemoresistance

    Poster Presenter(s)

  • Elaine Lee (she/her/hers)

    PhD Candidate
    University of Chicago Pritzker School of Molecular Engineering, United States

Introduction:

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to chemoresistance [1]. Previous studies show that abnormal nutrient levels in the PDAC tumor microenvironment (TME) suppress tumor cell apoptosis by promoting dependence on the pro-survival protein BCL-XL [2]. Therapeutic BCL-XL inhibition was shown to sensitize chemoresistant PDAC to gemcitabine, but systemic drug delivery is limited by on-target thrombocytopenia [2,3]. Here, iRGD-targeted PEG-ss-PPS polymersomes (PSOMs) are engineered to deliver BCL-XL-specific BH3 mimetics to PDAC tumors, enhancing tumor penetration and drug efficacy while attenuating toxicity.

Learning Objectives:

  • Explain how tumor targeted BH3 mimetic delivery may reduce thrombocytopenia risk versus systemic treatment
  • Analyze how iRGD functionalization and PSOM design parameters enable intracellular delivery to PDAC cells
  • Evaluate cellular uptake and intracellular cargo release of iRGD functionalized PSOMs in TME mimicking PDAC models