Cyano-modulated Zn(II)-Schiff base complexes for lysosome-targeted fluorescence imaging and pH-responsive camptothecin delivery.

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