Tumor-Targeted Polymer Theranostics for Navigated Surgery, Photodynamic Therapy and Tumor Imaging

In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice.<br/>Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. Moreover, theranostics, which links therapy and diagnostics, are widely studied for the disease treatment and the generation of diagnostic information using one multi-functional system. Recently, photodynamic therapy (PDT) has arised as a smart approach which employs the light irradiation to activate photosensitizers in situ after the selective tumor accumulation. Here, the exogenous light stimulus induces the formation of cytotoxic oxygen free radicals, i.e., singlet oxygen species (¹O₂), resulting in the cell death.<br/>In this work, polymer platform suitable for efficient stimuli-sensitive therapeutics, diagnostics and even theranostics based on water-soluble and amphiphilic polymer conjugates is presented. Synthetic nanocarriers based on methacrylamide-based copolymers are highly attractive for <i>in vivo</i> application as they are fully biocompatible, water soluble and non-toxic biomaterials with tailored physico-chemical properties for application in medicine. Their favorable pharmacokinetics altogether with Enhanced Permeability and Retention effect-driven tumor accumulation enable a higher uptake in solid tumors with an enhanced therapeutic outcome. The set of polymer biomaterials differing in their inner structure, molecular weight and functionality was designed, synthesized and evaluated for their therapeutic, diagnostic and even theranostic properties. The presented work will comprise the synthetic strategy of polymer materials and their utilization as the carrier of the therapeutically or/and diagnostically active molecules. Within this aproach selected photosensitizers were used for the development of tumor-targeted theranostics for both efficient tumor imaging and PDT. Their physico-chemical, <i>in vitro</i>, and <i>in vivo</i> behavior were investigated and the results indicate that the attachment of the hydrophobic photosensitizer molecule results in the formation of micelles, which protects the active molecules during its transport. The cytotoxicity of developed polymer nanomedicines was remarkably increased when light was irradiated and they showed high tumor targeted accumulation based on the EPR effect, therefore these polymer systems are promising candidates for tumor diagnostics and treatment.