Synthesis and in vitro assessment of gold nanoparticles conjugated with extracts, sterols and pure compounds derived from marine sponges from the Indian and Pacific Oceans†

Gold nanoparticles (AuNPs) exhibit different physical properties compared to small molecules, bulk materials and other nanoparticles. Their synthesis using plant extracts, particularly polyflavonoids as phytoreductants, for the conversion of Au(III) into Au(0) has been reported. In this study, AuNPs were synthesized with extracts, sterols and pure compounds derived from marine sponges using gold(III) chloride trihydrate. Extracts, hexane (JDH) and ethyl acetate (JDE), sterols (JC-2) and jaspamide were obtained from Jaspis diastra. Pure compounds, namely, contignasterol, ansellone A, motuporamines A and MN100 (a synthetic analog of pelorol), were also used. JC-2 was characterized using NMR and GC-MS, and the major constituent was determined to be β-sitosterol. β-Sitosterol has shown great promise as an anti-cancer molecule, but its poor aqueous solubility and bioavailability coupled with low targeting efficacy limit its therapeutic efficacy. Transmission electron microscopy (TEM) images revealed the formation of spherical AuNPs conjugated with JDH, JDE, JC-2, ansellone and contignasterol with average diameters of 21.1 ± 3.0 nm, 20.7 ± 2.1 nm, 26.2 ± 1.2 nm, 33.3 ± 5.1 nm and 30.8 ± 5.5 nm, respectively. No particle formation was seen with motuporamines A and MN100. Zeta potential values indicated that AuNPs-JC-2 was more stable than AuNPs-JDE, AuNPs-JDH and AuNPs-ansellone. Based on IC₅₀ values, the cytotoxicity of AuNPs-JDH increased in A172, TERA, HeLa and HepG2 cells but showed similar activity in HaCaT cells compared to JDH. The cytotoxicity of AuNPs-JDE decreased in A172 and HaCaT cells but increased in TERA1, HeLa and HepG2 cells compared to JDE. AuNPs-JC-2 showed enhanced cytotoxicity with a decrease in IC₅₀ values from 3.37 ± 0.19 μg mL⁻¹ to 0.52 ± 0.09 μg mL⁻¹ in A172 and from 2.28 ± 0.20 μg mL⁻¹ to 0.78 ± 0.28 μg mL⁻¹ in TERA1 compared to JC-2. The synergistic action of sterols in AuNPs-JC-2 seemed to favour enhanced anti-cancer activity. The presence of sterols increased the ability of transforming Au(III) into Au(0) to form AuNPs and further enhancing cellular uptake and, thus, anti-cancer activity. AuNPs-contignasterol displayed lower activity than contignasterol in the A172 cell line. No significant difference in activity was observed with AuNPs-ansellone A in the A172 and HaCaT cell lines compared to ansellone A.