Biological and Terahertz-Derived Signatures of Polymer Nanocarrier-Induced Cellular Responses: Toward Structure–Response Relationships in Photodynamic Therapy
Abstract
Polymer micelles based on poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) are widely investigated as nanocarriers for photodynamic therapy (PDT) due to their ability to solubilize hydrophobic photosensitizers such as pheophorbide a and enhance their delivery. In this study, we systematically assessed the impact of the morphology (spherical PEO5000-PCL4000 micelles vs PEO2000-PCL7000 worm-like nanovectors) and crosslinking status on PDT responses in both 2D cell cultures and 3D spheroid models. Although all pheophorbide-loaded formulations produced comparable phototoxicity in normal human dermal fibroblasts, human HCT-116 tumor cells, and canine MDCK-1 epithelial cells, detailed mechanistic analyses revealed distinct early cellular responses. Viability assays, membrane integrity measurements, ion homeostasis analyses, scanning electron microscopy, and terahertz (THz) spectroscopy demonstrated rapid membrane permeabilization, ionic imbalance, and ultrastructural remodeling following PDT. Worm-like nanovectors induced more pronounced membrane vesiculation, while THz spectroscopy revealed formulation-dependent membrane dynamics. Unexpectedly, blank nanovectors also altered ionic homeostasis and cellular behavior, indicating that these carriers are not biologically inert. Multivariate analyses integrating biological and THz-derived physical parameters generated distinctive signatures of nanocarrier formulations, enabling discrimination according to cargo loading, morphology, and crosslinking status. Together, these findings establish a multidimensional framework for characterizing nanocarrier effects on cells and highlight the value of combining biological and biophysical measurements to guide the rational design of PDT nanomedicines.
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BibTeX
@article{campion2026biological,
title = {{Biological and Terahertz-Derived Signatures of Polymer Nanocarrier-Induced Cellular Responses: Toward Structure–Response Relationships in Photodynamic Therapy}},
author = {Tiffany Campion and Blandine Lordon and Loïc Alauzet and Alexandre Wodrinski and Isabelle Fourquaux and Jean-Luc Putaux and Stéphanie Balor and Patricia Vicendo and Anne-Françoise Mingotaud and Guilhem Gallot and Laure Gibot},
journal = {ACS Applied Bio Materials},
year = {2026},
month = nov,
doi = {10.1021/acsabm.6c01407},
url = {https://hal.science/hal-05856671v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Biological and Terahertz-Derived Signatures of Polymer Nanocarrier-Induced Cellular Responses: Toward Structure–Response Relationships in Photodynamic Therapy
AU - Tiffany Campion
AU - Blandine Lordon
AU - Loïc Alauzet
AU - Alexandre Wodrinski
AU - Isabelle Fourquaux
AU - Jean-Luc Putaux
AU - Stéphanie Balor
AU - Patricia Vicendo
AU - Anne-Françoise Mingotaud
AU - Guilhem Gallot
AU - Laure Gibot
PY - 2026
DA - 2026/11/04
JO - ACS Applied Bio Materials
DO - 10.1021/acsabm.6c01407
UR - https://hal.science/hal-05856671v1
AB - Polymer micelles based on poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) are widely investigated as nanocarriers for photodynamic therapy (PDT) due to their ability to solubilize hydrophobic photosensitizers such as pheophorbide a and enhance their delivery. In this study, we systematically assessed the impact of the morphology (spherical PEO5000-PCL4000 micelles vs PEO2000-PCL7000 worm-like nanovectors) and crosslinking status on PDT responses in both 2D cell cultures and 3D spheroid models. Although all pheophorbide-loaded formulations produced comparable phototoxicity in normal human dermal fibroblasts, human HCT-116 tumor cells, and canine MDCK-1 epithelial cells, detailed mechanistic analyses revealed distinct early cellular responses. Viability assays, membrane integrity measurements, ion homeostasis analyses, scanning electron microscopy, and terahertz (THz) spectroscopy demonstrated rapid membrane permeabilization, ionic imbalance, and ultrastructural remodeling following PDT. Worm-like nanovectors induced more pronounced membrane vesiculation, while THz spectroscopy revealed formulation-dependent membrane dynamics. Unexpectedly, blank nanovectors also altered ionic homeostasis and cellular behavior, indicating that these carriers are not biologically inert. Multivariate analyses integrating biological and THz-derived physical parameters generated distinctive signatures of nanocarrier formulations, enabling discrimination according to cargo loading, morphology, and crosslinking status. Together, these findings establish a multidimensional framework for characterizing nanocarrier effects on cells and highlight the value of combining biological and biophysical measurements to guide the rational design of PDT nanomedicines.
SN - 2576-6422
ER -