Furin-Mediated Intracellular Self-Assembly of Olsalazine Nanoparticles for Enhanced Magnetic Resonance Imaging and Tumor Therapy

One strategy to enhance tumor retention of imaging agents or anti-cancer drugs is rational design of probes that undergo a tumor-specific enzymatic reaction which prevents them from being pumped out of the cell. Here, the anticancer agent olsalazine (Olsa) was conjugated to the cell-penetrating peptide RVRR. Taking advantage of a biologically compatible condensation reaction, single Olsa-RVRR molecules were self-assembled into large intracellular nanoparticles (Olsa-NPs) by the tumor-associated enzyme furin. Both Olsa-RVRR and Olsa-NPs could be readily detected with chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) by virtue of exchangeable olsalazine hydroxyl protons. In vivo studies using HCT116 and LoVo murine xenografts showed that the OlsaCEST signal and anti-tumor therapeutic effect were 6.5-fold and 5.2-fold increased, respectively, compared to olsalazine without RVRR, with an excellent “theranostic correlation” (R(2)=0.97) between the imaging signal and therapeutic response (normalized tumor size). This furin-targeted MRI-detectable platform has potential for imaging tumor aggressiveness, drug accumulation, and therapeutic response.