PUBLICATION
A ratiometric theranostic nanoplatform with acid-triggered drug release and glutathione-activated fluorescence turn-on
- Authors
- Flores-Cruz, R.D., Figueroa-DePaz, Y., Lobita, M.C., Hernández-Ayala, L.F., López-Pacheco, A.P., Dijkstra, E., Ruiz-Azuara, L., Santos, H.A.
- ID
- ZDB-PUB-251012-10
- Date
- 2025
- Source
- Journal of controlled release : official journal of the Controlled Release Society : 114309114309 (Journal)
- Registered Authors
- Keywords
- Cancer, Glutathione depletion, Ratiometric response, Theragnostics, Tumor detection
- MeSH Terms
-
- Animals
- Antineoplastic Agents*/administration & dosage
- Antineoplastic Agents*/chemistry
- Cell Line, Tumor
- Coordination Complexes*/administration & dosage
- Coordination Complexes*/chemistry
- Copper/administration & dosage
- Copper/chemistry
- Drug Delivery Systems
- Drug Liberation
- Female
- Fluorescence
- Fluorescent Dyes/administration & dosage
- Fluorescent Dyes/chemistry
- Folic Acid/chemistry
- Glutathione*/chemistry
- Glutathione*/metabolism
- Humans
- Quantum Dots/administration & dosage
- Quantum Dots/chemistry
- Theranostic Nanomedicine/methods
- Zebrafish
- Zinc Oxide/administration & dosage
- Zinc Oxide/chemistry
- PubMed
- 41076139 Full text @ J. Control Release
Citation
Flores-Cruz, R.D., Figueroa-DePaz, Y., Lobita, M.C., Hernández-Ayala, L.F., López-Pacheco, A.P., Dijkstra, E., Ruiz-Azuara, L., Santos, H.A. (2025) A ratiometric theranostic nanoplatform with acid-triggered drug release and glutathione-activated fluorescence turn-on. Journal of controlled release : official journal of the Controlled Release Society. :114309114309.
Abstract
Theragnostic nanomedicines that precisely coordinate drug delivery with imaging remain a significant challenge. Here, we report a novel nanoformulation that integrates acid-sensitive drug release with a glutathione (GSH)-activated fluorescence turn-on mechanism for targeted cancer therapy and real-time tracking. Our system is based on folic acid-functionalized zinc oxide quantum dots (QFZnO) loaded with a third-generation Casiopeina drug, IIIGCas, a copper-based coordination compound. Upon reaching the acidic tumor microenvironment, IIIGCas is released, subsequent intracellular GSH reduction converts the non-fluorescent Cu(II) complex into a highly fluorescent Cu(I) adduct, activating a distinct "turn-ON" signal. Computational studies reveal that this redox switch suppresses photoinduced electron transfer, restoring the emission of the drug's intrinsic curcumin-derived fluorophore and amplifying its fluorescence by sixfold. This mechanism creates a dual-emission system, enabling the simultaneous ratiometric tracking of nanocarrier (QFZnO) localization and drug activation. The nanoplatform demonstrated enhanced potency, showing statistically significant cytotoxicity in cervical and triple-negative breast cancer cell lines at far lower doses than free IIIGCas. In vivo, using zebrafish xenograft models, it achieved precise tumor targeting and a 90 % reduction in primary tumor area, while effectively illuminating secondary micrometastases. This work provides a generalizable blueprint for designing intelligent metal-complex delivery systems that optically report their own therapeutic activation in real-time.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping