The development of high-Z based metallic nanomaterials as radiosensitizers are limited due to having some challenges such as nonideal selectivity to the target tissue. In this work, we prepared X-ray triggered Bi 2 S 3 -Au heterodimers with a Schottky barrier and hopeful capability of the generation of free radicals for selectively improving radiotherapeutic efficacy in the tumors via not complicated and environmentally friendly methods. We explain the use of folic acid (FA) functionalized, BSA-modified Bi 2 S 3 -Au heterodimers (i.e., Bi 2 S 3 -Au-BSA-FA hybrids) as a targeted radiosensitizer for breast cancer therapy in the murine model. In addition to that, FA could give a tumor targeting ability, and the BSA coating could prolong circulation time ability to this hybrid system. The FA functionalized Bi 2 S 3 -Au heterodimer demonstrated in vitro and in vivo tumor enhanced radio sensitization. When the tumors were irradiated 24 h after receiving the Bi 2 S 3 -Au-BSA-FA hybrids, not only significant tumor inhibition was seen but also the survival ratio was increased in mice. Furthermore, the tumor bearing mice experienced a more effective tumor rejection when they received Bi 2 S 3 -Au-BSA-FA hybrids + X-ray irradiation than both of the Bi 2 S 3 -BSA + X-ray and Au + X-ray groups.

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Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi 2 S 3 –Au, with deep level defects (DLDs) in Bi 2 S 3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi 2 S 3 –Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

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The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research.