Determining water content in polymeric nano-particles to understand the mechanism behind chelator-free radiolabelling

Polymeric nanoparticles have significant applications in cancer treatment as carriers for chemotherapeutic drugs, leveraging the Enhanced Permeation and Retention (EPR) effect to target tumors. This effect, linked to the abnormal vasculature and lack of lymphatic drainage in tumors, varies among tumor types and patients, necessitating prior assessment for effective nanoparticle-based chemotherapy. Imaging techniques like SPECT, PET, or MRI can determine nanoparticle accumulation in tumors, requiring particles to be radiolabelled or loaded with contrast agents. We developed a chelator-free radiolabelling method that preserves particle properties by radiolabelling the micellar core, which works well with PEO-PCL polymers but less so with PEO-PB. Higher metal concentrations cause solid deposits in micelles, and radiolabelling efficiency peaks around one hour. Collaborating with TU Delft and Wageningen University, we found this method also applies to PLGA nanoparticles. Elemental speciation of the metal salt is critical, with metal hydroxide complexes essential for effective loading and stability. The mechanism of these complexes entering the hydrophobic core remains unclear, but water content in nanoparticles appears crucial. Understanding water exchange and transport in model systems could elucidate the radiolabelling mechanism and guide polymer selection for improved efficacy.