Tumor Targeted Albumin Coated Bismuth Sulfide Nanoparticles (Bi2S3) as Radiosensitizers and Carriers of Curcumin for Enhanced Chemoradiation Therapy

ACS Biomater Sci Eng. 2019 Sep 9;5(9):4416-4424. doi: 10.1021/acsbiomaterials.9b00489. Epub 2019 Aug 22.

Abstract

Combination therapy such as radiotherapy combined with chemotherapy has attracted excessive interest in the new cancer research area. Therefore, developing nanobiomaterials for combination of radiotherapy and chemotherapy is required for more powerful and successful cures. Because of the amazing X-ray sensitization proficiency of Bi based nanoparticles, in this work, we synthesized and used Bi2S3 as an enhancer of X-ray radiation therapy, and furthermore, Bi2S3 served as carrier of curcumin (CUR), a chemotherapy drug, for the goal of combination therapy. Additionally, we selected and conjugated folic acid (FA) as a targeting molecule for the direction of the designed system to the tumor site. After characterization of drug loaded FA conjugated Bi2S3@BSA nanoparticles (Bi2S3@BSA-FA-CUR) and in vitro and in vivo safety assessment, we applied it for enhanced chemotherapy and X-ray radiation therapy in cancer cells and a tumor bearing mice model. Moreover, the CT contrast ability of synthesized nanoparticles was examined. Here, we (1) for the first time developed the novel and targeted CUR loaded Bi2S3@BSA (Bi2S3@BSA-FA-CUR) to promote chemoradiation therapy in 4T1 cells and breast tumor in mice; (2) found the synthesized nanoparticles to have good stability; (3) injected a single dose of the designed radiosensitizer for cancer therapy; and (4) used a conventional X-ray dose, 2Gy, for X-ray radiation therapy. The result of in vivo X-ray radiotherapy shows that the mice tumors vanished near 3 weeks after radiation. Interestingly, these results show that Bi2S3@BSA-FA-CUR with the aid of X-ray can clearly promote the efficacy of chemoradiation therapy.

Keywords: CT imaging; X-ray sensitization; albumin; bismuth sulfide; chemoradiation; curcumin.