Theranostic silica nanoparticles for selective and simultaneous delivery of paclitaxel and coumarin to hypoxic tumors
Abstract
Theranostic nanomaterials, that combine diagnostic imaging with drug delivery, have emerged as a promising alternative to conventional oncology therapy. Tumor hypoxia and the poor solubility of chemotherapeutics like paclitaxel (PTX) remain critical obstacles in oncology. To address these challenges, we have developed hypoxia-responsive theranostic mesoporous silica nanoparticles for the selective delivery of PTX and a coumarin fluorescent dye to hypoxic tumors. The silica nanocarrier is capped with a molecular gate containing a masked coumarin fluorophore attached to a nitro-containing self-immolative spacer. Upon exposure to nitroreductases (NTR), enzymes overexpressed in hypoxic tumor microenvironments, the gate undergoes a self-immolation reaction, triggering the simultaneous release of the cargo and the activation of coumarin fluorescence. This design allows for real-time monitoring of drug release. In vitro assays demonstrated that the nanocarriers selectively reduced the viability of A549 lung cancer cells under hypoxic conditions while exhibiting high biocompatibility with healthy THP-1 macrophages in normoxia. Moreover, in vivo studies using a zebrafish xenograft model confirmed effective tumor accumulation and significant tumor regression (34% reduction) compared to controls, with reduced systemic toxicity. This proof-of-concept establishes the potential of these NTR-responsive theranostic MSNs as versatile multifunctional nanocarriers integrating diagnostic tracking with targeted therapeutic release in hypoxic environments.
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BibTeX
@article{rodrigomartinez2026theranostic,
title = {{Theranostic silica nanoparticles for selective and simultaneous delivery of paclitaxel and coumarin to hypoxic tumors}},
author = {Paula Rodrigo-Martínez and Lamiaa Mohamed Ahmed Ali and Carmen Coll and Magali Gary-Bobo and Jean-Yves Winum and Pau Arroyo and Jose Sáez and Pablo Gaviña},
journal = {International Journal of Pharmaceutics},
year = {2026},
month = sep,
doi = {10.1016/j.ijpharm.2026.127317},
url = {https://hal.science/hal-05735765v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Theranostic silica nanoparticles for selective and simultaneous delivery of paclitaxel and coumarin to hypoxic tumors
AU - Paula Rodrigo-Martínez
AU - Lamiaa Mohamed Ahmed Ali
AU - Carmen Coll
AU - Magali Gary-Bobo
AU - Jean-Yves Winum
AU - Pau Arroyo
AU - Jose Sáez
AU - Pablo Gaviña
PY - 2026
DA - 2026/09/02
JO - International Journal of Pharmaceutics
DO - 10.1016/j.ijpharm.2026.127317
UR - https://hal.science/hal-05735765v1
AB - Theranostic nanomaterials, that combine diagnostic imaging with drug delivery, have emerged as a promising alternative to conventional oncology therapy. Tumor hypoxia and the poor solubility of chemotherapeutics like paclitaxel (PTX) remain critical obstacles in oncology. To address these challenges, we have developed hypoxia-responsive theranostic mesoporous silica nanoparticles for the selective delivery of PTX and a coumarin fluorescent dye to hypoxic tumors. The silica nanocarrier is capped with a molecular gate containing a masked coumarin fluorophore attached to a nitro-containing self-immolative spacer. Upon exposure to nitroreductases (NTR), enzymes overexpressed in hypoxic tumor microenvironments, the gate undergoes a self-immolation reaction, triggering the simultaneous release of the cargo and the activation of coumarin fluorescence. This design allows for real-time monitoring of drug release. In vitro assays demonstrated that the nanocarriers selectively reduced the viability of A549 lung cancer cells under hypoxic conditions while exhibiting high biocompatibility with healthy THP-1 macrophages in normoxia. Moreover, in vivo studies using a zebrafish xenograft model confirmed effective tumor accumulation and significant tumor regression (34% reduction) compared to controls, with reduced systemic toxicity. This proof-of-concept establishes the potential of these NTR-responsive theranostic MSNs as versatile multifunctional nanocarriers integrating diagnostic tracking with targeted therapeutic release in hypoxic environments.
SN - 0378-5173
ER -