Synthesis and Characterization of Polymeric turn-on Probes for Real-Time Non-Invasive Optical Imaging

The great challenge for future precise therapy in oncology is exploring improved methodology for (i) early detection of small tumors, (ii) monitoring drug release at the target site in order to evaluate the treatment’s efficacy and (iii) detection of residual disease during surgery. The determination of the three is critical to the success of cancer therapy and improvement of patients’ survival rates. A diagnostic activatable nanosystem is an ideal platform to address these challenges.

In this study, we designed, synthesized and characterized a Turn-ON probe based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer. This probe is activated by cathepsin B, a lysosomal cysteine protease overexpressed in several tumor types. Our systems enable site-specific fluorophore activation to its Turn-ON state upon enzymatic degradation. This approach serves as a proof-of-concept for non-invasive real-time deep tissue intravital orthotopic monitoring that may potentially be exploited as a diagnostic tool in the clinic.