4.3 Article

Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines

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ELSEVIER
DOI: 10.1016/j.msec.2021.112078

Keywords

Genistein; Gold nanoparticles; Prostate carcinoma cells; Viability assay; Flow cytometry; Green nanotechnology

Funding

  1. Ministry of Science, Education and Technological Development of the Republic of Serbia, via Institute for Biological Research Sinisa Stankovic - National Institute of Republic of Serbia [451-03-68/2020-14/200007]
  2. Vinca Institute of Nuclear Sciences - National Institute of Republic of Serbia [451-03-68/2020-14/200017]

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The soy isoflavone genistein showed beneficial effects against prostate cancer cells in vitro and in vivo. However, its low bioavailability limited its use as a chemoprevention/therapeutic agent. Two variants of a new delivery system, genistein-gold nanoparticles conjugates Gen@AuNPs1 and Gen@AuNPs2, were synthesized using genistein to reduce Au3+ and stabilize the formed AuNPs. The nano-conjugates exhibited stability and bioactivity as an antioxidant and anti-prostate cancer agent with low toxicity against human primary cells.
Soy isoflavone genistein (Gen) exerts beneficial effects against prostate cancer cells in vitro and in vivo. However, its use as a chemoprevention/therapeutic agent is largely limited due to its low bioavailability. In this study we synthesized two variants of a new delivery system, genistein-gold nanoparticles conjugates Gen@AuNPs1 and Gen@AuNPs2, by an environmentally friendly method, using a dual role of Gen to reduce Au3+ and stabilize the formed AuNPs, with no additional component. The formation of Gen@AuNPs was confirmed via UV-Vis spectroscopy, FTIR, and Raman spectra measurements. The spherical shape and uniform size of Gen@AuNPs1 and Gen@AuNPs2 (10 +/- 2 and 23 +/- 3 nm, respectively), were determined by transmission electron microscopy. The nano-conjugates also varied in hydrodynamic diameter (65.0 +/- 1.7 and 153.0 +/- 2.2 nm) but had similar negative zeta potential (-35.0 +/- 2.5 and -37.0 +/- 1.6 mV), as measured by dynamic light scattering. The Gen loading was estimated to be 46 and 48%, for Gen@AuNPs1 and Gen@AuNPs2, respectively. The antiproliferative activities of GenAuNPs were confirmed by MTT test in vitro on three malignant prostate carcinoma cell lines (PC3, DU 145, and LNCaP), while selectivity toward malignant phenotype was confirmed using non-cancerous MRC-5 cells. Flow cytometric analysis showed that the inhibition on cell proliferation of more potent Gen@AuNPs1 nano-conjugate is comparable with the effects of free Gen. In conclusion, the obtained results, including physicochemical characterization of newly synthesized AuNPs loaded with Gen, cytotoxicity, and IC50 assessments, indicate their stability and bioactivity as an antioxidant and anti-prostate cancer agent, with low toxicity against human primary cells.

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