Synthesis and Characterization of Smart Polymeric Nanoprobes for Real-Time Optical Imaging

Theranostics describes any material for applications combining both therapy and diagnostics (1). The great challenge for future personalized therapy in oncology is exploring improved methodologies for (i) early detection of localized and disseminated tumor cells in patients and (ii) monitoring drug release at the target site in order to evaluate the treatment’s efficacy. The determination of both is critical to the success of cancer therapy and improvement of patients’ survival rates. A theranostic nanosystem composed of a nanocarrier, a drug and a Turn-ON probe is an ideal platform to address these challenges.

In this study, we designed, synthesized and characterized a theranostic nanomedicine based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer. The diagnostic system consists of self-quenched Cy5 and the therapeutic system is based on the anticancer agent paclitaxel (PTX). Both systems were conjugated to HPMA copolymer through a Gly-Phe-Leu-Gly (GFLG) linker, cleaved by cathepsin B, a lysosomal cysteine protease, overexpressed in several tumor types. Our systems enable site-specific release of the drug concomitantly with the fluorophore activation to its Turn-ON state upon enzymatic degradation (2). HPMA copolymer-PTX conjugate inhibited the proliferation of endothelial and breast cancer cells.

Our preliminary results with the diagnostic nano-conjugate HPMA copolymer-Cy5 present its potential use as a novel probe for sensing real-time drug release from the polymeric nanocarrier. This approach of co-delivery of two complementary systems serves as a proof-of-concept for non-invasive real-time deep tissue intravital orthotopic monitoring that may potentially be exploited as a theranostic nanomedicine in the clinic.

REFERENCES

1. S. S. Kelkar, T. M. Reineke, Bioconjugate chemistry 22, 1879 (Oct 19, 2011).
2. S. Ferber et al., Cancer letters, 352(1):81-9 (Mar 12, 2014).