Department of Pharmaceutics and Industrial Pharmacy Seminar, Title of the presentation: “Bioorthogonal pretargeting of multi-block cathepsin S-cleavable HPMA copolymers: In vitro and in vivo evaluations for improved ovarian cancer treatment”

We aimed to improve the radiotherapy of ovarian cancer by developing a polymeric delivery system, using HPMA copolymer as a carrier, that overcomes the current drawbacks of radiolabeled nanomedicine (e.g., retention in the mononuclear phagocyte system (MPS)-associated tissues and long circulation times needed for tumor targeting). The developed HPMA copolymeric system combines two strategies in one system. The first strategy is to enhance the clearance of retained large polymers in the MPS-associated tissues via biodegradation, by cathepsin S enzyme (Cat S) that is abundantly expressed in these tissues, into small and easily cleared fragments from the body. The second strategy is based on employing bioorthogonal in vivo chemistry between a trans-cyclooctene- (TCO) modified polymer and a tetrazine- (TZ) based radiotracer. Kinetic and in vitro Cat S studies were evaluated. In vivo studies were performed using a normal CF-1 and two ovarian cancer (SCID and NOD-SCID) mouse models. The kinetic studies revealed ultra-fast reactions between the developed TCO-tagged HPMA copolymer and the TZ-radiotracer, with the ability for the copolymer to be cleaved in vitro by Cat S. The in vivo studies showed biodegradation of the copolymer in the CF-1 mouse model with excellent in vivo TCO/TZ reactivity in ovarian cancer models resulted in improved tumor to non-target ratios observed. These results show the feasibility of this approach to enhance the treatment of ovarian cancer.

Link to the seminar: https://us.bbcollab.com/guest/d87702983c6144bdbb38ddf9e0a1e0a8