Saratov Fall Meeting - SFM'09 September 21 - 24, 2009, Saratov, Russia GOLD NANORODS AS NEW NANOCHROMOPHORES FOR PHOTOTHERMAL THERAPIES Roberto Pini, Fulvio Ratto, Paolo Matteini, Francesca Rossi Istituto di Fisica Applicata “Nello Carrara”, Consiglio Nazionale delle Ricerche, Sesto Fiorentino (Italy)
Motivations of this study Motivations of this study IFAC- IFAC -CNR CNR The biomedical use of gold nanoparticles activated by near The biomedical use of gold nanoparticles activated by near infrared (NIR) light is an intriguing perspective, which takes infrared (NIR) light is an intriguing perspective, which takes advantage of the good transmittance of biological tissues advantage of the good transmittance of biological tissues in a window between ~ 700 and 1300 nm in a window between ~ 700 and 1300 nm These nanoparticles may be delivered to selected tissues, These nanoparticles may be delivered to selected tissues, and then triggered from a remote NIR laser to perform and then triggered from a remote NIR laser to perform minimally invasive diagnostics, therapeutics and sensing minimally invasive diagnostics, therapeutics and sensing As a model example of photothermal therapy, we tested the As a model example of photothermal therapy, we tested the use of aqueous colloids of gold nanorods in the laser use of aqueous colloids of gold nanorods in the laser welding of eye tissues and arteries welding of eye tissues and arteries Perspectives on the use of gold nanoparticles in tumor Perspectives on the use of gold nanoparticles in tumor diagnostics and therapy will be also discussed diagnostics and therapy will be also discussed
Background Combination of near-infrared (NIR) lasers and NIR chromophores → Minimally invasive photothermal therapies Model therapy: NIR laser welding of connective tissues (already in the clinical phase in Ophthalmology) Standard NIR chromophores: organic dyes such as ICG, applied topically
Introducing laser welding of ocular tissues Introducing laser welding of ocular tissues Our approach: NIR laser + ICG Our approach: NIR laser + ICG IFAC- IFAC -CNR CNR Utilization of diode laser radiation at 810 nm (in both CW and Pulsed emissions) in association with the topical application of ICG (indocyanine green) as the photo-enhancing chromophore (optical absorption peak ~ 800 nm). Absorption spectrum Advantages in comparison with of ICG in corneal tissue other laser approaches: � Lower laser doses Diode laser (CW: ~ 100 mW, 12 W/cm 2 ) emission line (Pulsed: ~ 50 mJ, 100 ms) � localized welding only in presence of ICG
Our clinical experience in laser corneal Our clinical experience in laser corneal welding in penetrating, lamellar and welding in penetrating, lamellar and endothelial transplants endothelial transplants IFAC IFAC- -CNR CNR • Laser welding in substitution or as a support to conventional suturing • Combination with femtosecond laser corneal sculpturing • More than 100 corneal transplants in patients Advantages: • Lesser inflammation • Stable post-op astigmatism • Faster healing time Disadvantages: F.Rossi, P.Matteini, F.Ratto,L.Menabuoni, I.Lenzetti, R. Pini Laser tissue welding in ophthalmic surgery • ICG solution must be Journal of Biophotonics, 1 (4), pp. 331-342 (2008). prepared at time of surgery
Motivations for new chromophores ICG proved effective in many welding applications The range of biomedical applications of ICG is limited: Organic dyes suffer from: • Limited extinction efficiency; • Limited stability in the body; • Limited biochemical flexibility Objective: To replace organic dyes by innovative solutions → To extend their use to relevant applications, such as photothermal or photoacoustic treatment of cancer .
Gold nanorods Light irradiation excites localised + plasmon resonances → Near field enhancement (~800-fold E {Cubukcu, Appl. Phys. Lett. 89 , 093120 (2006)}) ; Rayleigh scattering; Optical absorption : Luminescence (e.g. e-h recombination) ( TPL - ~60 times brighter than rhodamine {Wang, Proc. Nat. Acad. Sci. 102 , 15752 (2005)}) ; Electron-phonon coupling… Pros: (Molar extinction higher by ~5 orders of magnitude than ICG {Jain, J. Phys. Chem. B 110 , 7238 (2006)}) • Extremely efficient; • Well stable; • Chemically flexible (e.g. for drug delivery) • Wavelength absorption at around 520 nm
Gold nanorods 11.4 nm r; 3.1 A.R. NIR radiation excites localised P.K. Jain et al. , J. Phys. Chem. B 110 , 7238 (2006) + plasmon resonances → Extinction Scattering Near field enhancement (~800-fold Absorption E {Cubukcu, Appl. Phys. Lett. 89 , 093120 (2006)}) ; 40 – 80 nm Rayleigh scattering; 10 – 20 nm 11.4 nm r; 3.9 A.R. Optical absorption : Luminescence (e.g. e-h recombination) ( TPL - ~60 times brighter than rhodamine {Wang, Proc. Nat. Acad. Sci. 102 , 15752 (2005)}) ; Electron-phonon coupling… Pros: (Molar extinction higher by ~5 orders of magnitude than ICG {Jain, J. Phys. Chem. B 110 , 7238 (2006)}) • Extremely efficient; • Well stable; • Chemically flexible (e.g. for drug delivery) • Wavelength tunable (in the range 700 nm – 1000 nm)
Introducing the new nanostructured nanostructured Introducing the new chromphores for NIR lasers: Gold Nanorods for NIR lasers: Gold Nanorods chromphores IFAC IFAC- -CNR CNR Colloidal gold nanorods have been synthesized in a seed-mediated approach from reduction of gold ions from HAuCl4 Typical sizes: 40-80 nm in length, 10-20 nm in width Exceptional optical absorption in the NIR is due to excitation of longitudinal surface plasmon resonances
11.4 nm r; 3.1 A.R. The Power of Gold Nanorods The Power of Gold Nanorods Extinction as novel NIR chromphores chromphores as novel NIR Scattering IFAC IFAC- -CNR CNR Absorption Comparison with organic chromophores: P.K. Jain et al. , J. Phys. Chem. B 110 , 7238 (2006) • Tuning of the NIR optical absorption 11.4 nm r; 3.9 A.R. peak, which depends on the ratio between length and width of the nanorod; • Greater efficiency: optical absorption coefficient ~ 5 orders of magnitude larger than ICG!!!; • Improved chemical and thermal stability; 21.9 nm r; 3.9 A.R. • Improved photo-bleaching threshold; • Possibility to target specific tissues via functionalization;
Biomedical applications of gold nanorods Therapeutics : Welding; Diagnostics : Hyperthermia; Scattering; Disruption Luminescence (incl. FLIM) ; Selectivity at the single-cell level! Photoacoustics Resolution at the single-cell level! Biosensing : Enhancement of Raman scattering (by up to 14 orders of magnitude {Arya, Phys. Rev. B 74 , 195438 (2006)}) ; And a variety of Enhancement of luminescence non biomedical applications…
Biomedical applications of gold nanorods: therapeutics The group of El-Sayed demonstrated the efficient and selective photothermal therapy of cancer cells irradiated by a CW near infrared laser. Gold nanorods conjugated with suitable antibodies are retained by the cancer cells selectively. As a consequence, much lower NIR laser fluences are required to induce a photothermal damage in the cancer cells (which retain the gold nanorods) than in the healthy cells (which do not retain the gold nanorods). X. Huang, I.H. El-Sayed, M.A. El-Sayed, J. Am. Chem. Soc. 128 , 2115 (2006) Photothermal
Biomedical applications of gold nanorods: therapeutics L. Tong, Y. Zhao, T.B. Huff, M.N. Hansen, A. Wei, J.X. Cheng, Adv. Mater. 19 , 3136 (2007) Photoacoustic The group of Wei demonstrated an even better efficiency and selectivity by the use of ultrashort NIR laser pulses, which induce a photoacoustic effect. Gold nanorods were conjugated with folate and therefore adhered to the membranes of the cancer cells selectively. Then cavitation micro-bubbles were produced under FS laser irradiation. These micro-bubbles disrupted the membrane of cancer cells, which causes immediate cell death or induced apoptosis.
Biomedical applications of gold nanorods: diagnostics H. Wang, T.B. Huff, D.A. Zweifel, W. He, P.S. Low, A. Wei, J.X. Cheng, PNAS 102, 15752 (2005) TPL H. Takahashi, T. Niidome, T. Kawano, S. Yamada, Y. Niidome, J. Nanopart. Res. 10, 221 (2008) Back scattering The group of Niidome (Japan) used gold nanorods conjugated with suitable The group of Wei demonstrated the antibodies as an efficient and selective possibility to image individual gold contrast agent to image cancer cells nanorods in a blood flow by two using darkfield microscopy photon luminescence. (which exploits the intense Rayleigh scattering from the gold nanorods).
Biomedical applications of gold nanorods: diagnostics M. Eghtedari, A. Oraevsky, J.A. Copland, N.A. Kotov, A. Conjusteau, M. Motamedi, Nano Lett. 7 , 1914 (2007) Photoacoustic The group of Alexander Oraevsky demonstrated the possibility to detect a Optoacoustic signal generated by photoacoustic signal from gold nanorods Au-NRs detected through a 4 cm at a concentration as low as ~ 1 pM. thick scattering media. Excitation induced by a ns NIR laser. This allowed to map the distribution of the The x-axis represents the time gold nanorods injected in a mouse. following triggering of laser pulse. Au-NRs were detectable at a concentration of 7.5·10 8 NRs per ml (1.25 pM).
Synthesis of gold nanorods Self-assembly of colloids of gold nanorods → Anisotropic overgrowth of gold nanoseeds Reduction of HAuCl 4 by ascorbic acid in the presence of CTAB → Highly sustainable process CTAB drives the shape anisotropy and stabilises the suspension
Recommend
More recommend
