Synthesis and biological evaluation of folate immobilized Si- 198 Au nanocomposites

Contents I.Introduction II.Experimental & Results -Silica ball synthesis -Carbon cage -Gold nanoparticles -Silica coated gold nanoparticles (SGNPs) -Octanol/water partition coefficient -In vitro & In vivo III.Conclusion

 Nanocomposites Introduction  Gold nanoparticles Drug delivery - Bioconjugate chem. 19(2008) Charge dependence of ligand release and monolayer stability of gold nanoparticles by biogenic thiols Photodynamic therapy -Cancer letters 239(2006) , Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles Electronics, Sensors, Probes, Catalysis Drug delivery systemCosmetic Electroplating Phosphor particle

198 Hg 197 Au (n, γ) 198 Au, T 1/2 =2.7d 0.985% (284.8 KeV) 98.99% (960.7 KeV) 0.025% ( KeV) γ γγ 0.159% (1087.7KeV) 96% (411.8KeV) Β-Β- Β-Β- Β-Β % (675.9KeV)  Decay scheme of 198 Au Reference: Statistics on the Radiation practices in korea (2011). Page Au 198 Au (n, γ) reaction

198 Au Passive targeting (size control of gold nanoparticle by carbon cage) Active targeting (Folate-nanocomposite) Tumor cell Endothelial cell Silica coated gold (Au-198) Surfactant-folate-silica coated gold (Au-198) Folate receptor Folate The Enhanced Permeability and Retention (EPR) effect

Pitch 10% HF + Ethanol N 2,12h TEOS/ NH 4 OH 700 ℃, 2h 800 ℃, 1h HAuCl 4 ∙nH 2 O Oxidation 900 ℃ / O 2 gas, 4h Folate EDC/NHS Surfactant Folate 197 Au(n, γ) 198 Au 198 Au Surfactant (tween 60) & Folate conjugated silica-gold composite nanoparticles

Silica ball synthesis EthanolNH 4 OHD.WTEOS 30 nm500 ml4 ml-30 ml 50 nm250 ml4 ml5 ml50 ml 70 nm250 ml10 ml4 ml50 ml 175 nm500 ml14 ml10.5 ml30 ml 400 nm300 ml14 ml28 ml20 ml Reference: Bong-Gyeom Kim et al., Chem. Eng., Vol.21, No. 6, December 2010, nm175 nm70 nm II.Experimental

Carbon cage Vacuum Filter (Solid: Pitch) Furnace 900 ℃ 4h Slowly add - PFO (Pyrolysis Fuel Oil) Methanol 800ml (50 ℃ ) Reference: Vishal J. Mayani et al.,, Separation and Purification Technolgy 80 (2011) h Stirring PFO Carbon Carbonization/N 2  Carbonization of pyrolysis fuel oil

Gold nanoparticles (GNPs) HAuCl 4 ·nH 2 ODMF (Dimethylformamide) 30 nm0.23 mM1150 ml 50 nm0.33 mM575 ml 150 nm0.5 mM345 ml 350 nm1.0 mM345 ml 30 nm50 nm Table 3. Gold nanoparticle of various size SEM image of gold nanoparticles 150 nm350 nm

 Silica coated gold nanoparticle Reference: Renyun Zhang et al., Materials Science and Engineering B 158 (2009) Scheme 3 2 h h h h TEM-EDS image of 2

FT-IR spectra of silica coated gold Au 38.16, 44.32, 64.54, Si XRD pattern of silica coated gold Si-OH (3448 cm -1 ) Si-O-Si (1113 cm -1 ) Si-OH (807 cm -1 ) OH (1627 cm -1 ) Silica

Solid state (CP-MAS) 13 C-NMR of FSGNPs Aromatic ( , , δ ppm) aliphatic regions (12-75 δ ppm) UV-Vis spectrum of FSGNPs FSGNPs Folate

Stability Characteristic Zeta potential(mV) Strong Agglomeration+5 to -5 Incipient Instability-10 to -30 Moderate Stability-31 to -40 Good Stability-41 to -60 Excellent Stability-61 and up Stability characteristic of zeta potential Size and Zeta potential of Tween 60-FSGNPs 50 nm mV H 2 O 3,920,285 cpm Octanol 867,095 cpm Log P Tween 60-FSGNPs (Au-198)

Biological test at 198 Au In vitro Cell uptake of surfactant-FSGNPs (CT-26 & SK-BR-3) (A) (B) (C) OpticalFluorescent Merge → Fluorescent image of the target as a result of the measurement KB and CT-26 in high could determine the uptake A549 KB CT-26

In vivo Biodistribution of surfactant-FSGNPs (CT-26 cancer)

Conclusion  Multi-functional hybrid nanocomposites have been synthesized by template method  Carbon cage was used to control the size of the gold nanoparticles.  we successfully carried out biological evaluation on various cancer cell lines with folate immobilized composite materials (FA-SGNPs)  SFS( 198 Au)GNPs has a possibilities as potential radiopharmaceuticals.