Phototherapy mode control by tuning molecular and supramolecular forms of indocyanine green in crosslinked polyion complex nanoparticles
Abstract
Photothermal therapy (PTT) offers a minimally invasive approach for treating hypoxic tumors, while photodynamic therapy (PDT) is limited by its oxygen dependence. Indocyanine green (ICG) is a clinically approved near-infrared (NIR) dye with potential for PTT and PDT, but its application is hindered by poor photostability, rapid clearance, and aggregation, resulting in unfavorable pharmacokinetics and limited phototherapeutic performances. Here, we address these limitations through a combination of chemical transformation of ICG by dimerization, controlled supramolecular assembly into dye aggregates, and a tailored formulation strategy. We systematically compared three forms, monomeric ICG, its covalent dimer (dICG), and the corresponding J-aggregate (dIJA), each formulated into polyion complex nanoparticles (PNPs) using poly(2-ethyl-2-oxazoline)-b-poly(L-ornithine) as the polyelectrolyte carrier matrix. Subsequent genipin-mediated core crosslinking produced crosslinked nanoparticles (CPNPs) with enhanced stability, high encapsulation efficiency, and preserved optical characteristics. CPNPs consistently outperformed free dye and non-crosslinked PNPs, showing improved colloidal stability, enhanced photostability, and higher photothermal performances. In FaDu cells, ICG-loaded CPNPs mediated oxygen-dependent photodynamic effects, whereas dICG- and dIJA-loaded CPNPs induced oxygen-independent photothermal cytotoxicity under NIR irradiation. Our integrated comparison demonstrates that controlling the molecular form and supramolecular assembly of ICG derivatives enables tunable NIR phototherapy, identifying dICG- and dIJA-based CPNPs as promising platforms for the treatment of hypoxic tumors by photoacoustic imaging (PAI) guided PTT.
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BibTeX
@article{aguileragarrido2026phototherapy,
title = {{Phototherapy mode control by tuning molecular and supramolecular forms of indocyanine green in crosslinked polyion complex nanoparticles}},
author = {Aixa Aguilera-Garrido and Marie Millard and Mathilde Bouché and Pascal Lemière and Nadia Canilho and Andreea Pasc and Kazunori Kataoka and Joachim F.R. van Guyse and Henri-Pierre Lassalle and Yann Bernhard},
journal = {Materials Today Advances},
year = {2026},
month = oct,
doi = {10.1016/j.mtadv.2026.100891},
url = {https://hal.science/hal-05704612v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Phototherapy mode control by tuning molecular and supramolecular forms of indocyanine green in crosslinked polyion complex nanoparticles
AU - Aixa Aguilera-Garrido
AU - Marie Millard
AU - Mathilde Bouché
AU - Pascal Lemière
AU - Nadia Canilho
AU - Andreea Pasc
AU - Kazunori Kataoka
AU - Joachim F.R. van Guyse
AU - Henri-Pierre Lassalle
AU - Yann Bernhard
PY - 2026
DA - 2026/10/13
JO - Materials Today Advances
DO - 10.1016/j.mtadv.2026.100891
UR - https://hal.science/hal-05704612v1
AB - Photothermal therapy (PTT) offers a minimally invasive approach for treating hypoxic tumors, while photodynamic therapy (PDT) is limited by its oxygen dependence. Indocyanine green (ICG) is a clinically approved near-infrared (NIR) dye with potential for PTT and PDT, but its application is hindered by poor photostability, rapid clearance, and aggregation, resulting in unfavorable pharmacokinetics and limited phototherapeutic performances. Here, we address these limitations through a combination of chemical transformation of ICG by dimerization, controlled supramolecular assembly into dye aggregates, and a tailored formulation strategy. We systematically compared three forms, monomeric ICG, its covalent dimer (dICG), and the corresponding J-aggregate (dIJA), each formulated into polyion complex nanoparticles (PNPs) using poly(2-ethyl-2-oxazoline)-b-poly(L-ornithine) as the polyelectrolyte carrier matrix. Subsequent genipin-mediated core crosslinking produced crosslinked nanoparticles (CPNPs) with enhanced stability, high encapsulation efficiency, and preserved optical characteristics. CPNPs consistently outperformed free dye and non-crosslinked PNPs, showing improved colloidal stability, enhanced photostability, and higher photothermal performances. In FaDu cells, ICG-loaded CPNPs mediated oxygen-dependent photodynamic effects, whereas dICG- and dIJA-loaded CPNPs induced oxygen-independent photothermal cytotoxicity under NIR irradiation. Our integrated comparison demonstrates that controlling the molecular form and supramolecular assembly of ICG derivatives enables tunable NIR phototherapy, identifying dICG- and dIJA-based CPNPs as promising platforms for the treatment of hypoxic tumors by photoacoustic imaging (PAI) guided PTT.
SN - 2590-0498
ER -