Design and synthesis of hydrolyzable coumarin-naphthalimide dual probes for NIR fluorescence detection and selective photodynamic activity in cancer cells.
5 affiliations
- 1Laboratorio de Cinética y Fotoquímica, Facultad de Química y Biología, Universidad de Santiago de Chile Santiago Chile [email protected].
- 2Laboratorio de Química Supramolecular y Fotobiología, Departamento de Química Física, Escuela de Química, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile Santiago Chile [email protected].
- 3Universidad Mayor, Facultad de Ciencias, Ingeniería y Tecnología, Centro de Nanotecnología Aplicada Camino La Pirámide 5750 Huechuraba 8580745 Santiago Chile.
- 4Universidad de Panamá, Facultad de Ciencias Naturales, Exactas y Tecnología, Departamento de Bioquímica Panamá 0824 República de Panamá.
- 5Sistema Nacional de Investigación (SNI), Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT) Panamá República de Panamá.
Abstract
Developing multifunctional agents capable of combining diagnostic and therapeutic functions remains a major challenge in cancer research. Herein, we report the design, synthesis, and photophysical characterization of a family of dual probes (C-NAF) based on coumarin-naphthalimide hybrids linked through an imine bond, combining near-infrared (NIR) fluorescence with light-induced cytotoxicity. C-NAF derivatives exhibit broad NIR emission and pronounced sensitivity to microenvironmental polarity, arising from locally excited (LE) and intramolecular charge-transfer (ICT) states modulated by solvent polarity. In their intact form, the C-NAF derivatives show negligible photodynamic activity. However, under polar protic conditions, imine hydrolysis generates photoactive naphthalimide aldehydes (NAF). Intracellular ROS detection and selective scavenger experiments indicate that the photodynamic response proceeds predominantly through a type I pathway involving radical-mediated ROS generation. Functionalization with butyl, morpholine, and biotin moieties was introduced to modulate physicochemical and molecular-recognition properties. In vitro studies in MCF-7 breast cancer cells showed that C-NAF derivatives are non-toxic in the dark and exhibit negligible phototoxicity under 540 nm irradiation, whereas significant phototoxicity occurs under 460 nm irradiation, consistent with photoactivity of the NAF hydrolysis products. C-NAF-B7 exhibited the strongest phototoxic response in MCF-7 cells, suggesting a possible contribution of the biotin moiety to cellular recognition or uptake. Conversely, negligible phototoxicity was observed in HEK-293 cells. Overall, these results identify C-NAF derivatives as promising dual probes combining NIR fluorescence with hydrolysis-activated, predominantly type I photodynamic activity and preferential photoactivity toward cancer cells under investigated conditions.
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BibTeX
@article{zunigasalazar2026design,
title = {{Design and synthesis of hydrolyzable coumarin-naphthalimide dual probes for NIR fluorescence detection and selective photodynamic activity in cancer cells.}},
author = {Benjamín Zúñiga-Salazar and Paula S Rivero-Jerez and Sofía Pérez-Del Pino and Francisco Mura and Pablo Barrias and Martín Canals Díaz and José Robinson-Duggon and Alexis Aspée and Denis Fuentealba and Daniel Zúñiga-Núñez},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra08240h},
url = {https://europepmc.org/article/MED/42898981},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design and synthesis of hydrolyzable coumarin-naphthalimide dual probes for NIR fluorescence detection and selective photodynamic activity in cancer cells.
AU - Benjamín Zúñiga-Salazar
AU - Paula S Rivero-Jerez
AU - Sofía Pérez-Del Pino
AU - Francisco Mura
AU - Pablo Barrias
AU - Martín Canals Díaz
AU - José Robinson-Duggon
AU - Alexis Aspée
AU - Denis Fuentealba
AU - Daniel Zúñiga-Núñez
PY - 2026
DA - 2026/10/19
JO - RSC advances
DO - 10.1039/d6ra08240h
UR - https://europepmc.org/article/MED/42898981
AB - Developing multifunctional agents capable of combining diagnostic and therapeutic functions remains a major challenge in cancer research. Herein, we report the design, synthesis, and photophysical characterization of a family of dual probes (C-NAF) based on coumarin-naphthalimide hybrids linked through an imine bond, combining near-infrared (NIR) fluorescence with light-induced cytotoxicity. C-NAF derivatives exhibit broad NIR emission and pronounced sensitivity to microenvironmental polarity, arising from locally excited (LE) and intramolecular charge-transfer (ICT) states modulated by solvent polarity. In their intact form, the C-NAF derivatives show negligible photodynamic activity. However, under polar protic conditions, imine hydrolysis generates photoactive naphthalimide aldehydes (NAF). Intracellular ROS detection and selective scavenger experiments indicate that the photodynamic response proceeds predominantly through a type I pathway involving radical-mediated ROS generation. Functionalization with butyl, morpholine, and biotin moieties was introduced to modulate physicochemical and molecular-recognition properties. In vitro studies in MCF-7 breast cancer cells showed that C-NAF derivatives are non-toxic in the dark and exhibit negligible phototoxicity under 540 nm irradiation, whereas significant phototoxicity occurs under 460 nm irradiation, consistent with photoactivity of the NAF hydrolysis products. C-NAF-B7 exhibited the strongest phototoxic response in MCF-7 cells, suggesting a possible contribution of the biotin moiety to cellular recognition or uptake. Conversely, negligible phototoxicity was observed in HEK-293 cells. Overall, these results identify C-NAF derivatives as promising dual probes combining NIR fluorescence with hydrolysis-activated, predominantly type I photodynamic activity and preferential photoactivity toward cancer cells under investigated conditions.
SN - 2046-2069
ER -