Background and Methods. : Despite the recent introduction of targeted bio-drugs, the scarcity of successful therapeutic options for advanced colorectal cancer remains a limiting factor in patient management. The efficacy of curative surgical interventions can only be extended through an earlier detection of metastatic foci, which is dependent on both the sensitivity and specificity of the diagnostic tools. Results. : Here we propose a high-performance imaging platform, based on Silica-Poly(Ethylene Glycol) Nanoparticles doped with Rhodamine B and Cyanine 5. A simultaneous detection of these dyes is the basis for background subtraction and signal amplification, thus providing high-sensitivity imaging. The functionalization of the Poly(Ethylene Glycol) tails on the external face of the nanoparticles with metastasis-specific peptides guarantees their homing to, and accumulation into at the target tissues, resulting in specific visualization even of sub-millimetric metastases. Conclusions. : The results here reported here demonstrate that our rationally-designed modular nano-systems have the characteristics ability to produce a real breakthrough in the detection of micrometastases, for subsequent to betranslated translation into to the clinics in the near immediate future.
M. Soster, R. Juris, S. Bonacchi, D. Genovese, M. Montalti, E. Rampazzo, et al. (2012). Targeted dual-color silica nanoparticles provide univocal identification of micrometastases in preclinical models of colorectal cancer. INTERNATIONAL JOURNAL OF NANOMEDICINE, 7, 4797-4807 [10.2147/IJN.S33825].
Targeted dual-color silica nanoparticles provide univocal identification of micrometastases in preclinical models of colorectal cancer
JURIS, RICCARDO;BONACCHI, SARA;GENOVESE, DAMIANO;MONTALTI, MARCO;RAMPAZZO, ENRICO;ZACCHERONI, NELSI;GARAGNANI, PAOLO;PRODI, LUCA;
2012
Abstract
Background and Methods. : Despite the recent introduction of targeted bio-drugs, the scarcity of successful therapeutic options for advanced colorectal cancer remains a limiting factor in patient management. The efficacy of curative surgical interventions can only be extended through an earlier detection of metastatic foci, which is dependent on both the sensitivity and specificity of the diagnostic tools. Results. : Here we propose a high-performance imaging platform, based on Silica-Poly(Ethylene Glycol) Nanoparticles doped with Rhodamine B and Cyanine 5. A simultaneous detection of these dyes is the basis for background subtraction and signal amplification, thus providing high-sensitivity imaging. The functionalization of the Poly(Ethylene Glycol) tails on the external face of the nanoparticles with metastasis-specific peptides guarantees their homing to, and accumulation into at the target tissues, resulting in specific visualization even of sub-millimetric metastases. Conclusions. : The results here reported here demonstrate that our rationally-designed modular nano-systems have the characteristics ability to produce a real breakthrough in the detection of micrometastases, for subsequent to betranslated translation into to the clinics in the near immediate future.File | Dimensione | Formato | |
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nanomedicine.pdf
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ijn-7-4797s1.tif
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Descrizione: Figure S1: Characterization of the fluorescent SPNs. (A) TEM analysis of SPN silica cores for the evaluation of size distribution. (B) Dynamic light scattering distribution of the nanoparticle hydrodynamic diameter. Exemplary graphs referred to CGIYRLRS-(Rhod)-SPNs are shown.
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Descrizione: Figure S2: Single-color targeted SPNs recognize human hepatic metastases ex vivo Frozen sections (10-μm ) of matched (grossly) normal liver and hepatic metastasis were fixed in 4% formaldehyde before being incubated with 5 × 1012 of either untargeted, CGIYRLRS-, or (A) CGVYSLRS-(Rhod)- or (B) (Cy5)-SPNs for 4 h at RT. After 3 washes in TBS-T, the SPN-emitted fluorescence was analyzed by confocal microscopy, and the output was converted in a false color LUT Fire scale for prompt visualization. The experiment was performed on specimens from 10 patients with metastatic CRC; exemplary images from tissues of patient #P85 are shown.
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