Low-concentration photodynamic therapy induces oxidative stress-driven cytoskeletal remodeling and formulation-dependent cell responses
Abstract
Photodynamic therapy (PDT) induces localized oxidative stress through the light-activated generation of reactive oxygen species (ROS), leading to targeted cell death. While conventional PDT protocols inducing marked photocytotoxicity have been extensively characterized, the cellular responses to low-concentration PDT, here defined as a reduced photosensitizer concentration under standard light fluence and irradiance, remain poorly understood. In this study, the effects of low-concentration PDT (0.33 µM) using pheophorbide a (Pheo), either in free form or encapsulated within poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) micelles, were examined in three cell models: primary human dermal fibroblasts, human HCT-116 carcinoma cells, and canine MDCK-1 epithelial cells. At the reduced Pheo concentration, PDT induced consistent morphological alterations across all models, including cytoskeletal remodeling, cell rounding, and early apoptotic features. These effects appeared earlier and were more pronounced with encapsulated Pheo, underscoring the influence of formulation on PDT efficiency. Antioxidant treatments (Sodium-L-ascorbate or N-Acetyl-L-cysteine) mitigated the morphological changes and cell death, supporting the involvement of oxidative stress in these responses. Compared with conventionally cytotoxic PDT, the low-concentration approach triggered slower cell-death dynamics, with caspase activation preceding plasma membrane permeabilization. Together, these findings show that lowconcentration PDT induces oxidative stress responses across diverse cell types, while their magnitude and kinetics remain formulation-dependent. These findings provide a framework for further investigating the temporal and mechanistic dimensions of PDT-induced oxidative stress and their potential relevance to photodynamic priming, immune modulation, and combination therapies.
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BibTeX
@article{campion2026lowconcentration,
title = {{Low-concentration photodynamic therapy induces oxidative stress-driven cytoskeletal remodeling and formulation-dependent cell responses}},
author = {Tiffany Campion and Loïc Alauzet and Isabelle Fourquaux and Patricia Vicendo and Anne-Françoise Mingotaud and Laure Gibot},
journal = {International Journal of Pharmaceutics},
year = {2026},
month = nov,
doi = {10.1016/j.ijpharm.2026.127632},
url = {https://hal.science/hal-05856639v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Low-concentration photodynamic therapy induces oxidative stress-driven cytoskeletal remodeling and formulation-dependent cell responses
AU - Tiffany Campion
AU - Loïc Alauzet
AU - Isabelle Fourquaux
AU - Patricia Vicendo
AU - Anne-Françoise Mingotaud
AU - Laure Gibot
PY - 2026
DA - 2026/11/03
JO - International Journal of Pharmaceutics
DO - 10.1016/j.ijpharm.2026.127632
UR - https://hal.science/hal-05856639v1
AB - Photodynamic therapy (PDT) induces localized oxidative stress through the light-activated generation of reactive oxygen species (ROS), leading to targeted cell death. While conventional PDT protocols inducing marked photocytotoxicity have been extensively characterized, the cellular responses to low-concentration PDT, here defined as a reduced photosensitizer concentration under standard light fluence and irradiance, remain poorly understood. In this study, the effects of low-concentration PDT (0.33 µM) using pheophorbide a (Pheo), either in free form or encapsulated within poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) micelles, were examined in three cell models: primary human dermal fibroblasts, human HCT-116 carcinoma cells, and canine MDCK-1 epithelial cells. At the reduced Pheo concentration, PDT induced consistent morphological alterations across all models, including cytoskeletal remodeling, cell rounding, and early apoptotic features. These effects appeared earlier and were more pronounced with encapsulated Pheo, underscoring the influence of formulation on PDT efficiency. Antioxidant treatments (Sodium-L-ascorbate or N-Acetyl-L-cysteine) mitigated the morphological changes and cell death, supporting the involvement of oxidative stress in these responses. Compared with conventionally cytotoxic PDT, the low-concentration approach triggered slower cell-death dynamics, with caspase activation preceding plasma membrane permeabilization. Together, these findings show that lowconcentration PDT induces oxidative stress responses across diverse cell types, while their magnitude and kinetics remain formulation-dependent. These findings provide a framework for further investigating the temporal and mechanistic dimensions of PDT-induced oxidative stress and their potential relevance to photodynamic priming, immune modulation, and combination therapies.
SN - 0378-5173
ER -