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, metastasis and therapy response. Several lysosomal proteases are overexpressed in cancer. Theranostics usually refers to a combination of therapy and diagnostics. Combining an activatable, fluorescent imaging probe with a therapeutic agent on a protease-degradable delivery platform thereby forms a theranostic nanomedicine. We developed a novel theranostic nanoprobe based on cathepsin B-biodegradable polymeric nanocarrier Polyglutamic Acid (PGA) bearing the chemotherapeutic drug paclitaxel (PTX) and Self-Quenched Cyanine NIR fluorophore (SQ-Cy5) as a diagnostic probe. 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 cancer cells. Our platform can be an appropriate candidate as research tool for real-time, intravital monitoring with potential clinical utility.