1,8-Naphthalimide-Based Multifunctional Compounds as Cu²⁺ Probes, Lysosome Staining Agents, and Non-viral Vectors

A series of multifunctional compounds (MFCs) 1a-1d based on 1,8-naphthalimide moiety were designed and synthesized. Due to the good fluorescence property and nucleic acid binding ability of 1,8-naphthalimide, these MFCs were applied in Cu²⁺ ion recognition, lysosome staining as well as RNA delivery. It was found that these MFCs exhibited highly selective fluorescence turn-off for Cu²⁺ in aqueous solution. The fluorescence emission of 1a-1d was quenched by a factor of 116-, 20-, 12-, and 14-fold in the presence of Cu²⁺ ions, respectively. Most importantly, 1a-Cu and 1b-Cu could be used as imaging reagents for detection of lysosome in live human cervical cancer cells (HeLa) using fluorescence microscopy. Furthermore, in order to evaluate the RNA delivery ability of 1a-1d, cellular uptake experiments were performed in HeLa, HepG2, U2Os, and MC3T3-E1 cell lines. The results showed that all the materials could deliver Cy5-labled RNA into the targeted cells. Among them, compound 1d modified with long hydrophobic chain exhibited the best RNA delivery efficiency in the four tested cell lines, and the performance was far better than lipofectamine 2000 and 25 kDa PEI, indicating the potential application in non-viral vectors.