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BIOE Seminar Series: Youngjae You (University of Buffalo) Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet Oxygen Sensitive Linker and PK/PD Modeling Light-activatable drug delivery strategy is an attractive approach for controlling local and regional tumors. This approach can be complementary to primary treatment options without causing systemic side effects. Photodynamic therapy (PDT) is one such a regimen, which has been used in the clinic for various tumors. However, the therapeutic efficacy of PDT is limited by various factors leading to incomplete tumor ablation for certain cases. The spatial and temporal limits of the major effector of PDT, singlet oxygen, have been suggested as possible causes of incomplete ablation in highly heterogeneous tumor and PDT. We recently developed a prodrug strategy that could overcome these limits by using a unique combination of PDT and site-specific chemotherapy. The prodrug is composed of a photosensitizer and anticancer drugs via a singlet oxygen-cleavable linker. In particular, we designed the prodrugs using fluorescent photosensitizers. Thus, the prodrugs can be imaged using optical imaging both in vitro and in vivo. We hypothesized that synergistic effects are made due to the complimentary PKPD characteristics of PDT and locally released anticancer drugs without systemic side effects. Upon illumination, the prodrugs cause immediate PDT damage and sustained damage by locally released anticancer drugs, which are released during the illumination at the target. Recent progress in our research will be presented at the presentation, for optimizing treatment conditions based on PB/PKPD modeling to achieve long term and complete cure of a small and a large tumor with external and interstitial beam illumination. Youngjae You (University of Buffalo)
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