Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC)

V. Karimnia; L. Huang; F. J. Slack; S. N. Bhatia; J. P. Celli

doi:10.1117/12.2610411

4 March 2022 Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC)

V. Karimnia, L. Huang, F. J. Slack, S. N. Bhatia, J. P. Celli

Author Affiliations +

Proceedings Volume 11940, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX; 1194005 (2022) https://doi.org/10.1117/12.2610411
Event: SPIE BiOS, 2022, San Francisco, California, United States

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human malignancies. PDAC is characterized by dense fibrous stroma which obstructs drug delivery and plays complex tumor-promoting roles through paracrine crosstalk. Photodynamic Therapy (PDT) is a light-based modality which has been demonstrated to be clinically feasible and effective for tumors of the pancreas. Here, we use in vitro heterocellular 3D co-culture models in conjunction with imaging, bulk rheology and microrheology methods to investigate the impact of verteporfin-based PDT on non-cellular (ECM) components of PDAC stroma. By measuring the rheology of ECM before and after PDT we find that softening of ECM is concomitant with an increase in transport of nanoparticles (NPs). At the same time, as shown previously, photodestruction of stromal fibroblasts, leads to enhanced tumor response to PDT. Collectively these results in 3D tumor models suggest that photodynamic stromal depletion (PSD) could be used to enhance subsequent drug delivery and improve tumor response to treatment.

Conference Presentation

Citation Download Citation

V. Karimnia, L. Huang, F. J. Slack, S. N. Bhatia, and J. P. Celli "Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC)", Proc. SPIE 11940, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX, 1194005 (4 March 2022); https://doi.org/10.1117/12.2610411

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