A 1,8-naphthalimide-[12]aneN3 derivative for efficient Cu2+ recognition, lysosome staining and siRNA delivery.

Development of multifunctional compounds as both fluorescence probes and non-viral vectors is still difficult till date. It is necessary to overcome many hurdles such as the balance of hydrophilic and hydrophobic moieties, binding affinity between multifunctional compound and targeting substrate, the cytotoxicity of multifunctional compound, and so on. In this work, the performances of compound 1 on Cu2+ recognition, lysosome staining and siRNA (small interfering RNA) delivery were investigated. It was found that compound 1 exhibited high selectivity and sensitivity toward Cu2+ in aqueous solutions. The fluorescence emission of 1 was quenched by a factor of 42-fold in the presence of Cu2+ ions. Even in the common pure organic solutions, still more than 8-fold fluorescence quenching was achieved. Due to its high sensitivity to the pH, the complex of 1-Cu was also successfully applied in selective staining of lysosome in HeLa cells. Furthermore, cellular uptake experiment revealed that compound 1 showed good RNA delivery ability in HeLa, HepG2, U2Os and MC3T3-E1 cells, and its performance was better than commercial agents lipofectamine 2000 and 25 kDa PEI (Polyethylenimine). The RNA interference effect mediated by compound 1 was further evaluated by real-time fluorescent quantitative PCR experiment. Compound 1 showed much higher transfection efficacy than lipofectamine 2000 in MC3T3-E1 cells. Our study demonstrated that 1,8-naphthalimide- [12]aneN3 compound 1 with low cytotoxicity, high specificity towards Cu2+ and lysosome, high transfection efficacy, and low cost is an efficient multifunctional material both in molecular recognition and gene delivery.