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

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

Physics

University of Massachusetts Boston
Harvard University

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

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.

Original language	English
Title of host publication	Optical Methods for Tumor Treatment and Detection
Subtitle of host publication	Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX
Editors	David H. Kessel, Tayyaba Hasan
Publisher	SPIE
ISBN (Electronic)	9781510647510
DOIs	https://doi.org/10.1117/12.2610411
State	Published - 2022
Event	Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX 2022 - Virtual, Online Duration: Feb 20 2022 → Feb 24 2022

Publication series

Name	Progress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume	11940
ISSN (Print)	1605-7422

Conference

Conference	Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX 2022
City	Virtual, Online
Period	2/20/22 → 2/24/22

ASJC Scopus Subject Areas

Electronic, Optical and Magnetic Materials
Atomic and Molecular Physics, and Optics
Biomaterials
Radiology Nuclear Medicine and imaging

Keywords

combination therapy
drug delivery
pancreatic ductal adenocarcinoma (PDAC)
Photodynamic Stromal Depletion (PSD)
photodynamic therapy

Access to Document

10.1117/12.2610411

Cite this

Karimnia, V., Huang, L., Slack, F. J., Bhatia, S. N., & Celli, J. P. (2022). Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC). In D. H. Kessel, & T. Hasan (Eds.), Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX Article 1194005 (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 11940). SPIE. https://doi.org/10.1117/12.2610411

Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC). / Karimnia, V.; Huang, L.; Slack, F. J. et al.
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX. ed. / David H. Kessel; Tayyaba Hasan. SPIE, 2022. 1194005 (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 11940).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Karimnia, V, Huang, L, Slack, FJ, Bhatia, SN & Celli, JP 2022, Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC). in DH Kessel & T Hasan (eds), Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX., 1194005, Progress in Biomedical Optics and Imaging - Proceedings of SPIE, vol. 11940, SPIE, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX 2022, Virtual, Online, 2/20/22. https://doi.org/10.1117/12.2610411

Karimnia V, Huang L, Slack FJ, Bhatia SN, Celli JP. Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC). In Kessel DH, Hasan T, editors, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX. SPIE. 2022. 1194005. (Progress in Biomedical Optics and Imaging - Proceedings of SPIE). doi: 10.1117/12.2610411

Karimnia, V. ; Huang, L. ; Slack, F. J. et al. / Evaluation of photodynamic stromal depletion (PSD) to enhance nanoparticle delivery in 3D models of pancreatic ductal adenocarcinoma (PDAC). Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic and Photobiomodulation Therapy XXX. editor / David H. Kessel ; Tayyaba Hasan. SPIE, 2022. (Progress in Biomedical Optics and Imaging - Proceedings of SPIE).

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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.",

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N2 - 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.

AB - 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.

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

Abstract

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Conference

ASJC Scopus Subject Areas

Keywords

Access to Document

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