HPMA-Based Nanomaterials as Tumor-Targeted Theranostics

Nanocarriers based on <i>N</i>-(2-hydroxypropyl)methacrylamide (HPMA) copolymers are attractive for <i>in vivo</i> application as they are fully biocompatible, water soluble and non-toxic. Their favorable pharmacokinetics allows a higher accumulation in solid tumors, thus improving the outcome of the cancer therapy. This work involves the synthesis of HPMA-based nanomaterials carrying the photosensitizer pyropheophorbide-a (PyF), affording well-defined polymer-based tumor-targeted theranostics. PyF derivatives were covalently attached to HPMA copolymers, which were previously synthesized by the controlled reversible addition-fragmentation chain transfer (RAFT) polymerization. Their physico-chemical characteristics and biological behavior were investigated and the results indicate that the attachment of the hydrophobic photosensitizer resulted in the system’s self-assembly into micelles. The use of HPMA backbone allowed the solubilization of PyF, longer circulation time and a selective tumor accumulation by the Enhanced Permeability and Retention (EPR) effect. Light irradiation was employed to induce the formation of cytotoxic oxygen free radicals, i.e., singlet oxygen species (¹O₂), resulting in a remarkably increased cytotoxicity even when low doses were administered, therefore these conjugates are promising candidates for a targeted photodynamic therapy and tumor diagnostics.<br/><br/>Acknowledgements: We gratefully acknowledge the support of the Czech Science Foundation (project 19-01417S) and the Ministry of Education, Youth, and Sports of the Czech Republic within the Interexcellence program (project LTAUSA18083).