Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids

Published in: Cell & Bioscience

Authors: Aaron Sorrin, Anika Dasgupta, Kathryn McNaughton, Carla Arnau Del Valle, Keri Zhou, Cindy Liu, Dana M. Roque & Huang Chiao Huang

Within the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation.

In this study, a novel combination strategy was developed to address chemoresistance of pancreatic ductal adenocarcinoma and targeting multiple mechanisms by giving 1-2-3 punch to cancer cells with FDA approved agents: 1) irinotecan (TOP1 inhibitor) at subcytotoxic doses, 2) BPD as photosensitive molecule for photodynamic priming to improve irinotecan delivery into cancer cell, and 3) minocycline priming to inhibit DNA repair enzyme activity. Modulight’s lasers were used for photodynamic priming in 3D cancer models. Results showed that this combination strategy was significantly more effective than single agents in combination and reduced the needed chemotherapy dose.


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