Bismuth nanoparticles-enhanced proton therapy: Concept and biological assessment

Proton therapy presents an appealing radiotherapy modality for the treatment of deeply-seated and unresectable tumors, but it still needs additional means to enhance the localization and efficiency of therapeutic action. Here we explore the use of elemental bismuth nanoparticles (Bi NPs) as sensitizers for proton therapy enhancement. Spherical Bi NPs were prepared by the method of pulsed laser ablation, followed by their coating with Pluronic polymer to stabilize them in a physiological environment. We observed efficient apoptotic cell death after proton irradiation at the Bragg peak, which was explained by high proton stopping power and low work function of Bi. The maximal effect was observed for 3 Gy radiation and 50 μg/mL NPs dose with 97 % inhibition of tumor cell clonogenic activity. The strong therapeutic effect was confirmed in vivo using aggressive Sa37 sarcoma tumors in mice. We observed 60 % inhibition of primary tumor growth with a decrease of metastatic potential in popliteal and axillary lymph nodes. Combined with X-ray contrast properties and radiosensitizing functionalities, the proposed concept of Bi NPs-enhanced proton therapy promises a major upgrade for cancer therapy.