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A "schizophotonic" all-in-one nanoparticle coating for multiplexed SE(R)RS biomedical imaging.

Iacono P, Karabeber H, Kircher MF - Angew. Chem. Int. Ed. Engl. (2014)

Bottom Line: Traditional synthetic routes require high metal-dye affinities and are challenged by unfavorable electrostatic interactions and limited scalability.The integration of various SERS reporters into a biocompatible polymeric surface coating allows for controlled dye incorporation, high colloidal stability, and optimized in vivo circulation times.We demonstrate the capability of this all-in-one gold surface coating and SERS reporter for multiplexed lymph-node imaging.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065 (USA).

No MeSH data available.


a) Photographs (top) and SERS image (bottom) of axillary lymph nodes and forelimb after injections of Au@IR-pHPMA (3 nm, 10 μL). b) Photograph and overlying SERS image of axillary lymph nodes and surrounding tissue 24 h after multisite injections of Au@IR-pHPMA (red), Au@IR-pHPMA-a (green), and Au@IR-pHPMA-b (blue) (3 nm, 10 μL each).
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fig04: a) Photographs (top) and SERS image (bottom) of axillary lymph nodes and forelimb after injections of Au@IR-pHPMA (3 nm, 10 μL). b) Photograph and overlying SERS image of axillary lymph nodes and surrounding tissue 24 h after multisite injections of Au@IR-pHPMA (red), Au@IR-pHPMA-a (green), and Au@IR-pHPMA-b (blue) (3 nm, 10 μL each).

Mentions: With these viable SERS nanoprobes in hand, we sought to explore their capacity for imaging to identify the first (sentinel) lymph nodes after subcutaneous probe injection, a process that is analogous to techniques used routinely during the treatment of most types of cancer.[25] Techniques such as radioactive tracer imaging and NIR fluorescence imaging, are current methods for sentinel lymph node mapping.[25] SERS imaging could prove vital to a surgeon in mapping these lymph nodes with improved accuracy, because it provides higher resolution than radioactive methods, and higher signal specificity (no autofluorescence) than fluorescence methods. In our experiments, non-tumor bearing nude mice were administered Au@IR-pHPMA in an MES buffered solution (10 μL, 3 nm, pH 7.3) in the paw of the right forelimb, and sentinel lymph node uptake was monitored at 2 and 24 h. At 2 h, SERS imaging demonstrated that the nanoparticles were draining towards the sentinel lymph node, with signal being observed both in the injection site of the forelimb and in the lymph node itself (Figure 4 a). At 24 h we observed strong SERS signal in the axillary lymph node and slight signal in the forelimb, indicating that the particles had drained almost completely from the lymphatic ducts into the lymph node. As a proof of concept, we also synthesized a variant of Au@IR-pHPMA where the terminal anchoring group for the polymer on the gold surface was the untreated dithioester (DTE) chelate. Upon administration of these analogues (Au@IR-pHPMA-DTE), we noticed that although SERS signal was observed in the axillary lymph node at 2 h, negligible signal was observed at 24 h (Figure S16). We hypothesized that this signal diminishment was caused by particle degradation by disassociation of polymer dithioester group from the gold surface, suggesting the necessity for a covalent Au–S linkage to uphold longer term in vivo stability.


A "schizophotonic" all-in-one nanoparticle coating for multiplexed SE(R)RS biomedical imaging.

Iacono P, Karabeber H, Kircher MF - Angew. Chem. Int. Ed. Engl. (2014)

a) Photographs (top) and SERS image (bottom) of axillary lymph nodes and forelimb after injections of Au@IR-pHPMA (3 nm, 10 μL). b) Photograph and overlying SERS image of axillary lymph nodes and surrounding tissue 24 h after multisite injections of Au@IR-pHPMA (red), Au@IR-pHPMA-a (green), and Au@IR-pHPMA-b (blue) (3 nm, 10 μL each).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389888&req=5

fig04: a) Photographs (top) and SERS image (bottom) of axillary lymph nodes and forelimb after injections of Au@IR-pHPMA (3 nm, 10 μL). b) Photograph and overlying SERS image of axillary lymph nodes and surrounding tissue 24 h after multisite injections of Au@IR-pHPMA (red), Au@IR-pHPMA-a (green), and Au@IR-pHPMA-b (blue) (3 nm, 10 μL each).
Mentions: With these viable SERS nanoprobes in hand, we sought to explore their capacity for imaging to identify the first (sentinel) lymph nodes after subcutaneous probe injection, a process that is analogous to techniques used routinely during the treatment of most types of cancer.[25] Techniques such as radioactive tracer imaging and NIR fluorescence imaging, are current methods for sentinel lymph node mapping.[25] SERS imaging could prove vital to a surgeon in mapping these lymph nodes with improved accuracy, because it provides higher resolution than radioactive methods, and higher signal specificity (no autofluorescence) than fluorescence methods. In our experiments, non-tumor bearing nude mice were administered Au@IR-pHPMA in an MES buffered solution (10 μL, 3 nm, pH 7.3) in the paw of the right forelimb, and sentinel lymph node uptake was monitored at 2 and 24 h. At 2 h, SERS imaging demonstrated that the nanoparticles were draining towards the sentinel lymph node, with signal being observed both in the injection site of the forelimb and in the lymph node itself (Figure 4 a). At 24 h we observed strong SERS signal in the axillary lymph node and slight signal in the forelimb, indicating that the particles had drained almost completely from the lymphatic ducts into the lymph node. As a proof of concept, we also synthesized a variant of Au@IR-pHPMA where the terminal anchoring group for the polymer on the gold surface was the untreated dithioester (DTE) chelate. Upon administration of these analogues (Au@IR-pHPMA-DTE), we noticed that although SERS signal was observed in the axillary lymph node at 2 h, negligible signal was observed at 24 h (Figure S16). We hypothesized that this signal diminishment was caused by particle degradation by disassociation of polymer dithioester group from the gold surface, suggesting the necessity for a covalent Au–S linkage to uphold longer term in vivo stability.

Bottom Line: Traditional synthetic routes require high metal-dye affinities and are challenged by unfavorable electrostatic interactions and limited scalability.The integration of various SERS reporters into a biocompatible polymeric surface coating allows for controlled dye incorporation, high colloidal stability, and optimized in vivo circulation times.We demonstrate the capability of this all-in-one gold surface coating and SERS reporter for multiplexed lymph-node imaging.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065 (USA).

No MeSH data available.