Characterization of multifunctional β-cyclodextrin-coated Bi2O3 nanoparticles conjugated with curcumin for CT imaging-guided synergetic chemo-radiotherapy in breast cancer

Int J Pharm. 2024 Jun 25:659:124264. doi: 10.1016/j.ijpharm.2024.124264. Epub 2024 May 22.

Abstract

Nanotechnology-based diagnostic, and therapeutic approaches revolutionized the field of cancer detection, and treatment, offering tremendous potential for cost-effective interventions in the early stages of disease. This research synthesized bismuth oxide (Bi2O3) nanoparticles (NPs) that were modified with polycyclodextrin (PCD), and functionalized with glucose (Glu) to load curcumin (CUR) for CT imaging and chemo-radiotherapy applications in Breast Cancer. The prepared Bi2O3@PCD-CUR-Glu NPs underwent comprehensive characterization, encompassing various aspects, including cell migration, cytotoxicity, cellular uptake, blood compatibility, reactive oxygen species (ROS) generation ability, real-time PCR analysis, in-vivo safety assessment, in-vivo anti-tumor efficacy, as well as in-vitro CT contrast and X-ray RT enhancement evaluation. CT scan was conducted before and after (1 and 3 h) intravenous injection of Bi2O3@PCD-CUR-Glu NPs. Through the use of coupled plasma optical emission spectrometry (ICP-OES) analysis, the final prepared nanoparticle distribution in the Bab/c mice was assessed. The spherical NPs that were ultimately synthesized and had a diameter of around 80 nm demonstrated exceptional toxicity towards the SKBr-3 breast cancer cell line. The cell viability was at its lowest level after 48 h of exposure to a radiation dose of 2 Gy at a concentration of 100 µg/mL. The combined treatment involving using Bi2O3@PCD-CUR-Glu NPs along with X-ray radiation showed a substantial increase in the generation of ROS, specifically a remarkable 420 % growth. Gene expression analysis indicated that the expression levels of P53, and BAX pro-apoptotic genes were significantly increased. The in-vitro CT imaging analysis conducted unequivocally demonstrated the notable superiority of NPs over Omnipaque in terms of X-ray absorption capacity, a staggering 1.52-fold increase at 80 kVp. The resultsdemonstrated that the targeted Bi2O3@PCD-CUR-Glu NPs could enhance the visibility of a small mice tumor that is detectable by computed tomography and made visible through X-ray attenuation. Results suggested that Bi2O3@PCD-CUR-Glu NPs, integrated with CT imaging and chemo-radiotherapy, have great potential as a versatile theranostic system for clinical application.

Keywords: Bismuth oxide nanoparticles; Breast cancer; CT contrast agent; Radiotherapy; Targeting drug delivery.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Bismuth* / administration & dosage
  • Bismuth* / chemistry
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemoradiotherapy / methods
  • Curcumin* / administration & dosage
  • Curcumin* / chemistry
  • Curcumin* / pharmacology
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C*
  • Nanoparticles* / chemistry
  • Reactive Oxygen Species / metabolism
  • Tomography, X-Ray Computed* / methods
  • beta-Cyclodextrins* / chemistry

Substances

  • Curcumin
  • beta-Cyclodextrins
  • Bismuth
  • bismuth oxide
  • Reactive Oxygen Species
  • Antineoplastic Agents