Facile synthesis of biocompatible sub-5 nm alginate-stabilised gold nanoparticles with sonosensitising properties

Adilet Beishenaliev, Farid Nazer Faruqu, Bey Fen Leo, Lei Cheng Lit, Yean Leng Loke, Chia Ching Chang, Yin Yin Teo*, Zamri Chik, Yiing Yee Foo, Lip Yong Chung, Lik Voon Kiew

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The use of ultrasmall gold nanoparticles (usAuNPs, diameters <5 nm) in cancer diagnosis and therapy has been increasing due to their unique tumour tissue/cell penetrating traits and renal-excretable properties. In order to produce usAuNPs with narrow polydispersity, toxic stabilising agents were normally coated on usAuNP surface during their synthesis. This has necessitated post-synthesis surface modification to minimise stabilising-agent-related toxicity in order to qualify usAuNPs for in vivo use. Nevertheless, the average sizes of usAuNPs that were surface-modified using the reported methods were often found to be above the renal filtration threshold (5 nm), hence limiting their renal excretion and suitability for in vivo use. Here, we report a novel and facile synthesis of biocompatible and renal-clearable usAuNPs using sodium alginate as the stabilising agent. The alginate-stabilised usAuNPs (usAuNPsALG) had an average size of 4.5 ± 0.2 nm with narrow polydispersity (0.21), a zeta potential of −30.4 mV, and were stable in water for up to 45 days. They were haemocompatible and non-toxic in vitro at concentrations up to 100 μg/ml (4T1 breast cancer cells). Further, usAuNPsALG were found to generate reactive oxygen species and exert dose-dependent sonotoxicity to 4T1 and MDA-MB-231 cells in vitro at a level equivalent to that of the larger AuNPs (>5 nm), but upon ultrasound irradiation at 2–4-fold lower frequency (1 MHz) and intensity (0.5 W/cm2) than those previously reported in AuNP-mediated SDT. This suggests the potential use of the usAuNPsALG as sonosensitising agents for anti-cancer adjunctive therapy. Overall, this study reported the novel method for the synthesis of biocompatible usAuNPs with considerable sonosensitising properties and the potential of these sub-5 nm nanoparticles for in vivo applications.

Original languageEnglish
Article number127141
JournalColloids and Surfaces A: Physicochemical and Engineering Aspects
StatePublished - 20 Oct 2021


  • Biocompatibility
  • Gold nanoparticles (AuNPs)
  • Reactive oxygen species
  • Sodium alginate
  • Sonodynamic therapy (SDT)


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