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

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.

Nanomedicine-based approaches for improved delivery of phyto-therapeutics for cancer therapy

“…Bi 2 S 3 nanoparticles could both sensitize X-ray proficiency and carry curcumin whereas the folate moiety enhanced the tumor accumulation of albumin nanoparticles. Therefore, intravenous injection of Bi 2 S 3 @ BSA-FA-CUR nanoparticles combined with X-ray radiation in tumor-bearing mice showed enhanced antitumor efficacy and significant tumor size reduction compared to single drug or radiation therapy [26].…”

Facile green synthesis of bismuth sulfide radiosensitizer via biomineralization of albumin natural molecule for chemoradiation therapy aim

“…Bi 2 S 3 @BSA HNPs was prepared as previously process [2,14]. 50 mM Bi (NO 3 ) 3 in 1.0 ml of HNO 3 solution (2 M) was slowly added into BSA solution (250 mg BSA in 8.0 ml deionized water) under vigorous stirring.…”

“…Recently, a novel BSA-mediated biomineralization method for achieving biocompatible Bi 2 S 3 NPs was reported [2,14]. The synthesis process is highlighted by two steps: (i) suitable conditions for facilitating the coordination of Bi 3þ cations with BSA and preventing the former from hydrolysis, (ii) pHmediated formation of Bi 2 S 3 HNPs upon a quick adjustment of the reaction pH up to 12.…”

“…Unlikely, high dose irradiation can damage normal tissues. High atomic number Z, nanoparticles can desirably enhance the photoelectric, Compton effects and radiation therapy efficacy [1,2]. In addition, by considering nanoparticles power, it is easy to concentrate the high atomic number particles in tumour tissues, and capable to enhance radiation therapy.…”

“…Moreover, recent years bismuth compound nanomaterials have attracted huge attention in this field as well. Bismuth is a typical high-Z element with a high X-ray attenuation coefficient (5.74 cm 2 .kg À1 at 100 keV) [6]. Obviously, the bismuth compounds have the X-ray computed tomography enhancement efficiency [7].…”