Cyano-modulated Zn(II)-Schiff base complexes for lysosome-targeted fluorescence imaging and pH-responsive camptothecin delivery
7 affiliations
- 1Department of Radiation Oncology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- 2Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, Zhejiang-Hong Kong Precision Theranostics of Thoracic Tumors Joint Laboratory, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- 3Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
- 4Joint Research Centre, HIM, The First Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China
- 5College of Medicine, Etugen University, Ulaanbaatar, Mongolia
- 6College of Materials Science and Engineering, Hunan University, Changsha, Hunan, China
- 7Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
Abstract
Integrating real-time diagnostic imaging with stimuli-responsive therapy into a single nanoplatform represents a core research direction in precision oncology. Nevertheless, the construction of a lysosome-targeted theranostic system that simultaneously combines high-contrast luminescence, biosafety, and spatially controlled drug release characteristics continues to pose formidable challenges. Herein, by modulating the number of electron-withdrawing cyano (–CN) substituents on the ligand backbone, a series of Zn(II)-Schiff base complexes—designated Zn-0CN, Zn-1CN, and Zn-2CN—were rationally designed and synthesized. The cyano-governed donor–acceptor topology induced a pronounced bathochromic shift in the emission spectra (497 nm for Zn-0CN versus 543 nm for Zn-2CN) while concurrently elevating the fluorescence quantum yield of Zn-2CN to 9.2%. Density functional theory calculations revealed that Zn(II) coordination narrows the HOMO–LUMO energy gap and enhances intramolecular charge transfer; notably, the bis-cyano-substituted Zn-2CN exhibited strong charge polarization within the metal-binding region. Zn-2CN nanoparticles selectively accumulated in the lysosomes of 4 T1 breast cancer cells, displaying bright yellow-green fluorescence and outstanding colocalization with a commercial lysosomal red probe. Following camptothecin (CPT) encapsulation, the resulting CPT@Zn-2CN nanoparticles achieved a cumulative drug release of 92% within 36 h at pH 5.6, whereas only 41% leaked at physiological pH 7.4, confirming their pH-triggered drug release capability. The bare Zn-2CN material exhibited negligible cytotoxicity (cell viability exceeding 90% at 100 μg·mL −1 ). At an equivalent CPT dosage (20 μg·mL −1 ), CPT@Zn-2CN elicited markedly superior apoptosis induction compared with free CPT (cell viabilities of 20.5% and 37.5%, respectively), an enhancement attributable to drug release activated by the acidic lysosomal milieu. This work establishes a versatile “imaging–drug delivery integration” platform based on Zn(II)-Schiff base chemistry, wherein a cyano-functionalization strategy enables precise tuning of photophysical properties, and the intrinsic pH sensitivity of the imine bond allows for lysosome-responsive drug release. This study demonstrates that such complexes can seamlessly combine bioimaging with microenvironment-responsive chemotherapy, offering a promising strategy for precision oncology.
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BibTeX
@article{zhang2026cyanomodulated,
title = {{Cyano-modulated Zn(II)-Schiff base complexes for lysosome-targeted fluorescence imaging and pH-responsive camptothecin delivery}},
author = {Xi Zhang and Wenjie Sun and Xin Li and Yuanzhe Li and Shuo Xiang and Lifang Zhang and Yiping Yang},
journal = {International Journal of Pharmaceutics X},
year = {2026},
month = jun,
doi = {10.1016/j.ijpx.2026.100594},
url = {https://doi.org/10.1016/j.ijpx.2026.100594},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Cyano-modulated Zn(II)-Schiff base complexes for lysosome-targeted fluorescence imaging and pH-responsive camptothecin delivery
AU - Xi Zhang
AU - Wenjie Sun
AU - Xin Li
AU - Yuanzhe Li
AU - Shuo Xiang
AU - Lifang Zhang
AU - Yiping Yang
PY - 2026
DA - 2026/06/29
JO - International Journal of Pharmaceutics X
DO - 10.1016/j.ijpx.2026.100594
UR - https://doi.org/10.1016/j.ijpx.2026.100594
AB - Integrating real-time diagnostic imaging with stimuli-responsive therapy into a single nanoplatform represents a core research direction in precision oncology. Nevertheless, the construction of a lysosome-targeted theranostic system that simultaneously combines high-contrast luminescence, biosafety, and spatially controlled drug release characteristics continues to pose formidable challenges. Herein, by modulating the number of electron-withdrawing cyano (–CN) substituents on the ligand backbone, a series of Zn(II)-Schiff base complexes—designated Zn-0CN, Zn-1CN, and Zn-2CN—were rationally designed and synthesized. The cyano-governed donor–acceptor topology induced a pronounced bathochromic shift in the emission spectra (497 nm for Zn-0CN versus 543 nm for Zn-2CN) while concurrently elevating the fluorescence quantum yield of Zn-2CN to 9.2%. Density functional theory calculations revealed that Zn(II) coordination narrows the HOMO–LUMO energy gap and enhances intramolecular charge transfer; notably, the bis-cyano-substituted Zn-2CN exhibited strong charge polarization within the metal-binding region. Zn-2CN nanoparticles selectively accumulated in the lysosomes of 4 T1 breast cancer cells, displaying bright yellow-green fluorescence and outstanding colocalization with a commercial lysosomal red probe. Following camptothecin (CPT) encapsulation, the resulting CPT@Zn-2CN nanoparticles achieved a cumulative drug release of 92% within 36 h at pH 5.6, whereas only 41% leaked at physiological pH 7.4, confirming their pH-triggered drug release capability. The bare Zn-2CN material exhibited negligible cytotoxicity (cell viability exceeding 90% at 100 μg·mL −1 ). At an equivalent CPT dosage (20 μg·mL −1 ), CPT@Zn-2CN elicited markedly superior apoptosis induction compared with free CPT (cell viabilities of 20.5% and 37.5%, respectively), an enhancement attributable to drug release activated by the acidic lysosomal milieu. This work establishes a versatile “imaging–drug delivery integration” platform based on Zn(II)-Schiff base chemistry, wherein a cyano-functionalization strategy enables precise tuning of photophysical properties, and the intrinsic pH sensitivity of the imine bond allows for lysosome-responsive drug release. This study demonstrates that such complexes can seamlessly combine bioimaging with microenvironment-responsive chemotherapy, offering a promising strategy for precision oncology.
SN - 2590-1567
ER -