Self-quenched liposomal probes for tumor imaging based on cellular on/off system

Near-infrared fluorophores have been widely used in tumor imaging due to superior resolution and sensitivity, high penetration depth and low auto-fluorescence. However, the tumor imaging efficacy of fluorophores in vivo is impeded by the background signals and the delivery efficiency of the fluorophores. To realize sensitive tumor imaging, we developed self-quenched liposomal probes DiR-LP-C and DiR-LP-B as tumor-specific imaging probes with cellular on/off system. To prepare DiR-LP-C probes, hydrophobic DiR was solubilized in DMSO and actively loaded into the aqueous interior of liposomes. Based on the structure, DiR-LP-C showed high self-quenching (46-fold at 1.0% loading ratio) that is ‘off’ state with weak fluorescence signal but recovered fluorescence after cellular uptake. DiR-LP-B was prepared where the hydrophobic DiR molecules were dispersed in the hydrophobic lipid bilayer of liposomes and showed weaker self-quenching (5.4-fold at 1.0% loading ratio). Importantly, DiR-LP-C showed brighter cell imaging than DiR-LP-B. For in vivo imaging, both probes showed excellent tumor targeting with signal to background ratio around 5 at 24 h post-injection, with DiR-LP-C had much lower background. These results proved that the tumor-homing cellular ‘on/off’ nanoparticle system of DiR-LP-C has a great potential for tumor imaging and phototherapeutics.