Lysosome-targeted theranostics: Integration of real-time fluorescence imaging and controlled drug delivery via Zn(II)-Schiff Base complexes

Abstract

The development of lysosome-targeted theranostic platforms stands at the forefront of precision oncology. However, significant challenges persist in synchronizing real-time diagnostic imaging with spatiotemporal controlled therapeutic delivery. Current systems commonly encounter issues such as suboptimal quantum yields, pH-insensitive release kinetics, and spectral interference between imaging and drug-tracking modes. To address these limitations, we rationally designed a novel series of Zn(II)-Schiff base complexes through coordination chemistry to achieve lysosomal targeting, enhanced optical properties, and microenvironment-responsive drug release. Optical characterization revealed significant red shifts in the absorption and emission spectra after Zn(II) coordination, which can be attributed to the reduction in energy bandgap. Among these complexes, Zn-((2,5-diamino-1,4-benzenedithiol dihydrochloride)-(2,4-Dihydroxybenzaldehyde)) (Zn-MTDH) exhibited the highest quantum yield (63.7 %) and enabled high-contrast lysosomal imaging in 4 T1 breast cancer cells, positioning it as a promising candidate for biological applications. When loaded with camptothecin (CPT), CPT@Zn-MTDH displayed pH-dependent drug release kinetics (81 % cumulative release at pH 5.6 vs. 51 % at pH 7.4 over 36 h). Cellular assays demonstrated that Zn-MTDH exhibits low cytotoxicity and excellent biocompatibility. In contrast, CPT@Zn-MTDH exhibited enhanced cytotoxicity compared to free CPT, highlighting the potential of these complexes for lysosome-targeted cancer therapy. This study establishes Zn(II)-Schiff base complexes as a versatile “track-and-treat” theranostic platform, thereby bridging diagnostic precision with therapeutic efficacy.