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 (Mo6) 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 Mo6 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 Mo6 cluster bearing azido ligands via a copper-free click reaction. The resulting nanosized Mo6 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 Mo6 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.