Journal of Materials Research and Technology (Nov 2020)

Immobilization of l-asparaginase on gold nanoparticles for novel drug delivery approach as anti-cancer agent against human breast carcinoma cells

  • Ali G. Al-Dulimi,
  • Ali Z. Al-Saffar,
  • Ghassan M. Sulaiman,
  • Khalil A.A. Khalil,
  • Khawla S. Khashan,
  • Hanady S.A. Al-Shmgani,
  • Elsadig M. Ahmed

Journal volume & issue
Vol. 9, no. 6
pp. 15394 – 15411

Abstract

Read online

l-asparaginase is an amidohydrolase enzyme that is widely identified as one of the most potential anti cancerous drugs. Nevertheless, this drug is poorly bioavailable and hence its pharmaceutical uses are limited. To improve its bioactivity, l-asparaginase was loaded on gold nanoparticles (GNPs) along with Arg-Gly-Asp (RGD) peptide that direct the enzyme to targeted cancer cells with aim to enhancing the anticancer efficiency. Successful preparation of GNPs and the conjugate (GNPs-PEG-l-asparaginase-RGD) was verified and delineated by employing UV–VIS spectrophotometer, FTIR, XRD, FE-SEM, and TEM. UV–VIS spectrophotometer, Fourier Transform Infrared (FT-IR), X-Ray Diffraction (XRD), Field Emission Scanning Electron Microscopic (FE-SEM), and Transmission Electron Microscopy (TEM). The efficiency of the GNPs and conjugate to target and distribute in MCF-7 cells was evaluated using high fluorescent signals and confirmed by fluorescence microscopy. A variety of parameters were tested to investigate the anticancer potential of each compound toward MCF-7 cells in vitro. The conjugate demonstrated significant antioxidant effects with high tumor targeting efficacy and distribution in MCF-7 cells. It caused a decrease in cell proliferation rate and clonogenicity of MCF-7 cells, while initiating apoptosis and promoting cell cycle arrest at the G2/M, as confirmed by flow cytometry analysis. These effects were coupled with upregulating the pro-apoptotic p53 while downregulating the anti-apoptotic Bcl-2, which resulted in an alleviation of the mitochondrial membrane potential (MMP) and, thereby, the secretion of cytochrome c. The outcomes of the present study propose the high feasibility for further development of the conjugate as a novel agent against cancer cells.

Keywords