Protease-Degradable Polymeric Nanomedicine Bearing Paclitaxel and a Turn-On Fluorescent Probe for Cancer Theranostics

The tumor microenvironment plays a crucial role in cancer progression and metastasis as well as in the way cancer responds to therapy. In particular, it is known that several lysosomal Cysteine proteases such as Cathepsin B, which participate in ECM degradation, are overexpressed in some cancer types.

Early detection of cancer and real-time monitoring of therapy response could provide a paramount opportunity for individualized therapy. Among different imaging modalities, optical imaging holds several advantages, although clinically available fluorescence-based imaging agents suffer from many limitations.

Theranostics is a relatively new term, introduced in 2002 (1), that describes any material for applications combining both therapy and diagnostics. Combining an activatable, fluorescent imaging probe with a therapeutic agent on a delivery platform such as polymers thereby forms a theranostic nanomedicine. This novel precision nanomedicine may overcome the fluorescence imaging probe limitations while providing real-time diagnostic and monitoring of drug release.

In our study, we designed and characterized a novel theranostic nanomedicine based on our widely studied, non-toxic polymeric nanocarrier Polyglutamic Acid (PGA) bearing the chemotherapeutic drug paclitaxel (PTX) and Self-Quenched Cyanine NIR fluorophore (SQ-Cy5) as a diagnostic probe. PGA backbone is biodegradable by cathepsin B. Our system enabled site-specific drug release concomitantly with the activation of the fluorophore to its Turn-ON state. Furthermore, PGA-PTX-SQ-Cy5 conjugate inhibited the proliferation, migration and formation of tubular-like structures of endothelial and different types of cancer cells.

Our platform described here can be an appropriate candidate to be used as research tool for real-time, intravital, deep tissue monitoring and may have clinical utility as a potential theranostic nanomedicine.

1. S. Ferber et al., Cancer letters, (Mar 12, 2014).