5 November 2012 Multifunctional plasmonic nanoparticles for biomedical applications Georgios A. Sotiriou, and Sotiris E. Pratsinis Particle Technology Laboratory, Department of Mechanical and Process Engineering Swiss Federal Institute of Technology Zurich (ETH Zurich), Switzerland
2 Plasmonic materials Noble metals (Gold, silver) Plasmons: Oscillation of surface conduction electron by electromagnetic radiation Silver is better than gold but also more toxic [1] Plasmon absorption band: depends Strongly scatter light [2] on refractive index surrounding [2] plasmonic particles [2] [1] [2] Dark field image of silver nanoparticles [1] Willets and Van Duyne, Annu. Rev. Phys. Chem. (2007), 58, 267. [2] McFarland and Van Duyne, Nano Letters (2003), 33, 1057.
3 Plasmonic (e.g. Au, Ag) particles in bioimaging : analyte : ligand (protein) binding event : plasmonic particle time (30 min)
4 Plasmonic (e.g. Au, Ag) particles in bioimaging [1] cancer cell cancer cell with particles on surface 50 mm Untagged Au nanoparticles time (30 min) Tagged Au nanoparticles [1] Aaron, Nitin, Travis, Kumar, Collier, Park, Jose-Yacaman, Coghlan, Follen, Richards-Kortum, Sokolov, J. Biomed. Opt. 12, 034007 (2007).
Multifunctional plasmonic-magnetic nanoparticles Hybrid plasmonic-magnetic nanostructures [1] : Dual imaging (microscopy, MRI) Magnetic separation Therapy (phototherapy, hyperthermia) [2] Fe 3 O 4 Core-shell (magnetic-plasmonic) Ag magnetic particle plasmonic particle Heterodimer (magnetic-plasmonic) Challenges: Toxicity? [3] Stability against flocculation [4] Many process-steps [1] Ag/Fe 3 O 4 heterodimers attached on macrophage cells [1] Sotiriou, WIREs Nanomed. Nanobiotechnol. in press, DOI: 10.1002/wnan.1190 (2012). [2] Jiang, Gu, Shao, Devlin, Papaefthymiou, Ying, Adv. Mater. 20, 4403 (2008). [3] Anker, Hall, Lyandres, Shah, Zhao Van Duyne, Nature Mater. 7, 442 (2008). [4] Ruenraroengsal, Cook, Florence, J. Control. Release 141, 265 (2010). 5
6 Hybrid plasmonic-magnetic nanoparticles - Synthesis Ag content x in xag/fe 2 O 3 Low x High x x = 0-50 wt% [1] Teleki, Heine, Krumeich, Akhtar Pratsinis, Langmuir 24, 12553 (2008). [2] Sotiriou, Sannomiya, Teleki, Krumeich, Vörös, Pratsinis, Adv. Funct. Mater. 20, 4250 (2010).
7 Hybrid Ag/Fe 2 O 3 nanostructures SiO 2 Ag Fe 2 O 3 Sotiriou, Hirt, Lozach, Teleki, Krumeich, Pratsinis, Chem. Mater. 23, 1985 (2011).
8 Magnetization of silica-coated Ag/Fe 2 O 3 SiO 2 Fe 2 O 3 Ag Comparable magnetization for pure flame-made Fe 2 O 3 [1] Lower magnetization for x = 50 wt% Ag Higher a-fe 2 O 3 content Near superparamagnetic behavior [1] Teleki, Suter, Kidambi, Ergeneman, Krumeich, Nelson, Pratsinis, Chem. Mater. 21, 2094 (2009).
9 Plasmonic properties Magnetic manipulation 2.0 SiO 2 Ag B = 0 Fe 2 O 3 B > 0 2.0 Mechanically mixed B = 0 B > 0 Absorbance, a.u. 1.5 1.0 0.5 x = 10 wt% 20 35 50 35Ag/Fe 2 O 3 B > 0 Ni-Cu-Ni magnet B = 0 Absorbance, a.u. 1.5 1.0 0.5 35Ag/Fe 2 O 3 B > 0 35Ag/Fe 2 O 3 Ni-Cu-Ni magnet 50Ag/Fe 2 O 3 B = 0 xag/fe 2 O 3 0.0 300 400 500 600 700 Wavelength, nm 0.0 300 400 500 600 700 Wavelength, nm
10 SiO 2 -coating: Inhibition of toxic Ag + ion release Ag + ion concentration, 15 10 5 Uncoated SiO 2 -coated open symbols: ISE filled : DGT de-ionized water 50 of Ag Uncoated: Higher release for smaller Ag size [1,2] SiO 2 -coating prevents Ag + ion release 0 0 10 20 30 40 50 60 Ag-content x in xag/fe 2 O 3, wt% [1] Sotiriou and Pratsinis, Environ. Sci. Technol. (2010), 44, 5649. [2] Sotiriou, Teleki, Camenzind, Krumeich, Meyer, Panke, Pratsinis, Chem. Eng. J. (2011), 170, 547.
11 Biocompatible hybrid nanoparticles (HeLa cells) 80 Drug (Staurosporin) after 24 hours Dead cells, % 60 40 35Ag/Fe 2 O 3 20 PBS 0 control positive 5 2.5 2.5 1.25 1.25 control + 0.625 0.625 control negative Ag Ag Ag Ag control -
Introduction Experimental Results and Discussion Conclusions Biofunctionalization Cell detection Raji cells Dl 10 nm Untagged Raji + labeled particles w/o antibody w/ " Absorbance, a.u. Ag Fe2O3 20 mm 35Ag/Fe2O3 SiO2 Tagged Raji + HeLa cells labeled particles Ag 20 mm Ag Fe2O3 Tagged HeLa + labeled particles Fe2O3 400 450 Wavelength, nm 500 20 mm20 mm 20 mm Sotiriou, Sannomiya, Teleki, Krumeich, Vörös, Pratsinis, Adv. Funct. Mater. 20, 4250 (2010). Sotiriou, Hirt, Lozach, Teleki, Krumeich, Pratsinis, Chem. Mater. 23, 1985 (2011). 05.11.2012 sotiriou@ptl.mavt.ethz.ch, Particle Technology Laboratory - ETH Zurich 12
13 Conclusions One-step synthesis of SiO 2 -coated Ag/Fe 2 O 3 Biocompatible hybrid nanoparticles 80 Drug (Staurosporin) after 24 hours Selective binding and detection of cells Tagged Raji + labeled particles Dead cells, % 60 40 20 0 35Ag/Fe 2 O 3 PBS control positive 5 2.5 2.5 1.25 1.25 control + 0.625 0.625 control negative Ag Ag Ag Ag control - SiO 2 coating prevents flocculation 20 mm
14 Outlook Surface biofunctionalization targeting cancer cells Photothermal treatment with IR laser In-vitro towards in-vivo Biofunctionalization with EGF Melanoma cells overexpressing EGF receptor Under nanophosphor excitation Under laser irradiation Sotiriou, Franco, Poulikakos, Ferrari, ACS Nano 6, 3888-3897 (2012).
15 Thank you for listening Sotiriou, Sannomiya, Teleki, Krumeich, Vörös, Pratsinis, Adv. Funct. Mater. (2010), 20, 4250. SiO 2 -coated nanosilver particles dispersed in water under dark-field illumination