Poster T7 - Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids

Thursday, October 24, 2024

10:00 AM – 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Anika Dasgupta (she/her/hers)

Undergraduate Research Assistant
University of Maryland, College Park
Olney, Maryland, United States

Co-Author(s)

AS

Aaron Sorrin

Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA, United States
Kathryn McNaughton

PhD student
Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA, United States
CA

Carla Arnau del Valle

Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA, United States
KZ

Keri Zhou

Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA, United States
CL

Cindy Liu

Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA, United States
Dana M. Roque, MD (she/her/hers)

Associate Professor, Division of Gynecologic Oncology
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA
Baltimore, Maryland, United States

Primary Investigator(s)

HH

Huang Chiao Huang

Associate Professor of Bioengineering
Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA, United States

Introduction: In the past decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have gained recognition as an effective treatment for various cancers. Preclinical studies have highlighted the promising synergy of PARPi with photodynamic therapy (PDT), a treatment modality that combines light and specialized light-activated dyes (photosensitizers) to generate reactive oxygen species and induce cancer cell death.

Materials and

Methods: In this study, the most potent clinically approved PARPi, talazoparib, is loaded into a polymeric nanoparticle (NP-Tal) and functionalized with antibody-photosensitizer conjugates (Photoimmunoconjugates, PICs) to form PIC-NP-Tal. NP-Tal are optimized by modulating synthesis parameters and interfaced with PICs via copper-free click chemistry for targeting and photoactivity capabilities. Concurrently, a new 3D fluorescent co-culture model is developed with the parental OVCAR-8-DsRed2 cell line and the chemo-resistant NCI/ADR-RES-EGFP subline. This model facilitates quantification of trends in evolutionary dynamics of chemoresistance acquired in response to various treatment regimens. The coculture model is treated with PIC-NP-Tal and relevant control groups and evaluated at multiple irradiation doses in order to characterize treatment effects on spheroid ablation and cell-line population dynamics.

Results, Conclusions, and Discussions: Our data show that at a low dosage (0.01μM), NP-Tal kills the parental cells and spares the chemoresistant sublime, driving chemoresistance. Results show powerful combination effects with regard to total spheroid ablation when PIC and NP-Tal are co-delivered, while conjugated PIC-NP-Tal demonstrates decreased efficacy. Additionally, cell population analysis demonstrates selection pressure towards the chemoresistant subline in all PIC-containing treatment groups. This study provides important insights into the synthesis parameters of PARPi-loaded polymeric nanoparticles and highlights the potential of PDT-based combination therapies in the context of acquired drug resistance.

Acknowledgements (Optional):