Radiosensitizing molybdenum iodide nanoclusters conjugated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer: a step towards radiodynamic therapy

Radiodynamic therapy treats deep-seated tumors by exploiting radiosensitizers (RSs) that are delivered to tumors and produce reactive oxygen species upon X-ray irradiation. Octahedral molybdenum clusters (Mo-6) have shown promise as RSs, but their direct administration is hampered by their limited stability and low solubility in the biological medium. Association of the Mo-6 clusters with organic polymers can overcome this issue and improve their bioavailability. Herein, we have conjugated a dibenzocyclooctyne-functionalized N-(2-hydroxypropyl)methacrylamide copolymer with a Mo-6 cluster bearing azido ligands via a copper-free click reaction. The resulting nanosized Mo-6 cluster/polymer conjugate exhibited long-term stability of its colloidal and luminescence properties in phosphate-buffered saline, and displayed photosensitized formation of singlet oxygen, affirming its potential for photodynamic processes. The conjugate was not toxic towards HeLa cells, demonstrated phototoxic effects upon blue-light irradiation, with an better therapeutic window than the bare Mo-6 cluster, and showed promise as an RS, enhancing cell growth suppression upon X-ray irradiation. Overall, this nanosystem constitutes a propitious theranostic tool for photo/radiodynamic applications.