Photodynamic therapy (PDT) has emerged as an attractive option for cancer treatment. However, conventional PDT is activated by light that has poor tissue penetration depths, limiting its applicability in the clinic. Recently the idea of using X-ray sources to activate PDT and overcome the shallow penetration issue has garnered significant interest. This can be achieved by external beam irradiation and using a nanoparticle scintillator as transducer. Alternatively, research on exploiting Cherenkov radiation from radioisotopes to activate PDT has also begun to flourish. In either approach, the most auspicious success is achieved using nanoparticles as either a scintillator or a photosensitizer to mediate energy transfer and radical production. Both X-ray induced PDT (X-PDT) and Cherenkov radiation PDT (CR-PDT) contain a significant radiation therapy (RT) component and are essentially PDT and RT combination. Unlike the conventional combination, however, in X-PDT and CR-PDT, one energy source simultaneously activates both processes, making the combination always in synchronism and the synergy potential maximized. While still in early stage of development, X-PDT and CR-PDT address important issues in the clinic and hold great potential in translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Iodine has shown promise in enhancing radiotherapy. However, conventional iodine compounds show fast clearance and low retention inside cancer cells, limiting their application as a radiosensitizer. Herein, we synthesize poly­(maleic anhydride-alt-1-octadecene) coated KI nanoparticles (PMAO-KI NPs) and evaluate their potential for enhancing radiotherapy. Owing to the polymer coating, the KI core of PMAO-KI NPs is not instantly dissolved in aqueous solutions but slowly degraded, allowing for controlled release of iodide (I–). I– is transported into cells via the sodium iodide symporter (NIS), which is upregulated in breast cancer cells. Our results show that PMAO-KI NPs can enhance radiation-induced production of reactive oxygen species such as hydroxyl radicals. When tested in vitro with MCF-7 cells, PMAO-KI NPs promote radiation-induced DNA double-strand breaks and lipid peroxidation, causing a drop in cancer cell viability and reproductivity. When tested in MCF-7 bearing mice, PMAO-KI NPs show significant radiosensitizing effects, leading to complete tumor eradication in 80% of the treated animals without inducing additional toxicity. Overall, our strategy exploits electrolyte nanoparticles to deliver iodide into cancer cells through NIS, thus promoting radiotherapy against breast cancer.

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