Phormidesmis communis strain AB_11_10 was isolated and identified using microscopy and 16s rRNA sequencing, and its phytochemical constituents were determined using liquid chromatography-quadrupole time-of-flight mass spectrometry. The isolate had a segmented filamentous shape with a blue-green color. Many biomolecules, including organic compounds, amino acids, and fatty acids, were detected. P. communis strain AB_11_10 was used to synthesize gold nanoparticles (Ph-AuNPs) by adjusting the optimum reaction conditions. The concentration, algal/precursor ratio, temperature, reaction time, and pH significantly influenced the synthesis of the Ph-AuNPs. Mixing 1 mL of 0.5 mM of HAuCl4 with 1 mL of algal extract and exposing the mixture to 100 °C for 30 min at pH 5.6 were the optimum conditions for the biosynthesis of Ph-AuNPs at a wavelength of 524.5 nm. The Ph-AuNPs were characterized using TEM, SEM, EDX, and mapping Zeta sizer and FTIR. The Ph-AuNPs had quasi-spherical to triangular shapes with an average diameter of 9.6 ± 4.3 nm. Ph-AuNPs composed of 76.10 ± 3.14% of Au and trace amounts of carbon and oxygen were detected, indicating that the P. communis strain AB_11_10 successfully synthesized Ph-AuNPs. The hydrodynamic diameter of the Ph-AuNPs was 28.5 nm, and their potential charge was -17.7 mV. O-H, N-H, C=C, N-O, C-H, and C-O were coated onto the surfaces of the Ph-AuNPs. These groups correspond to algal phytochemicals, which may have been the main reducing and stabilizing substances during the Ph-AuNP synthesis. The therapeutic activity of the Ph-AuNPs against osteosarcoma cancers was examined in MG-63 and SAOS-2 cell lines, while their biocompatibility was tested against Vero cell lines using a sulforhodamine B assay. The Ph-AuNPs had potent antitumor activity against the MG-63 and SAOS-2 cells, with a low toxicity toward Vero cells. Flow cytometry and cell cycle arrest analyses revealed that the Ph-AuNPs enhanced the apoptotic pathway and arrested the cell cycle in the MG-63 and SAOS-2 cells. P. communis strain AB_11_10 provides a new source to synthesize small, stable, and biocompatible AuNPs that act as apoptotic enhancers in osteosarcoma.
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