A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods

Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requirin...
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Autor*in:	Alfano, Massimo [verfasserIn] Alchera, Elisa Sacchi, Angelina Gori, Alessandro Quilici, Giacomo Locatelli, Irene Venegoni, Chiara Lucianò, Roberta Gasparri, Anna Maria Colombo, Barbara Taiè, Giulia Jose, Jithin Armanetti, Paolo Menichetti, Luca Musco, Giovanna Salonia, Andrea Corti, Angelo Curnis, Flavio

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	DGR motif α5β1 integrin Gold nanorods Photoacoustic imaging Bladder cancer

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Journal of nanobiotechnology - London : Biomed Central, 2003, 21(2023), 1 vom: 27. Aug.
Übergeordnetes Werk:	volume:21 ; year:2023 ; number:1 ; day:27 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s12951-023-02028-5

Katalog-ID:	SPR052890309

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100	1		\|a Alfano, Massimo \|e verfasserin \|4 aut
245	1	2	\|a A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
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520			\|a Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract
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allfields	10.1186/s12951-023-02028-5 doi (DE-627)SPR052890309 (SPR)s12951-023-02028-5-e DE-627 ger DE-627 rakwb eng Alfano, Massimo verfasserin aut A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract DGR motif (dpeaa)DE-He213 α5β1 integrin (dpeaa)DE-He213 Gold nanorods (dpeaa)DE-He213 Photoacoustic imaging (dpeaa)DE-He213 Bladder cancer (dpeaa)DE-He213 Alchera, Elisa aut Sacchi, Angelina aut Gori, Alessandro aut Quilici, Giacomo aut Locatelli, Irene aut Venegoni, Chiara aut Lucianò, Roberta aut Gasparri, Anna Maria aut Colombo, Barbara aut Taiè, Giulia aut Jose, Jithin aut Armanetti, Paolo aut Menichetti, Luca aut Musco, Giovanna aut Salonia, Andrea aut Corti, Angelo (orcid)0000-0002-0893-6191 aut Curnis, Flavio (orcid)0000-0002-7231-9569 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 21(2023), 1 vom: 27. Aug. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:21 year:2023 number:1 day:27 month:08 https://dx.doi.org/10.1186/s12951-023-02028-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 27 08
spelling	10.1186/s12951-023-02028-5 doi (DE-627)SPR052890309 (SPR)s12951-023-02028-5-e DE-627 ger DE-627 rakwb eng Alfano, Massimo verfasserin aut A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract DGR motif (dpeaa)DE-He213 α5β1 integrin (dpeaa)DE-He213 Gold nanorods (dpeaa)DE-He213 Photoacoustic imaging (dpeaa)DE-He213 Bladder cancer (dpeaa)DE-He213 Alchera, Elisa aut Sacchi, Angelina aut Gori, Alessandro aut Quilici, Giacomo aut Locatelli, Irene aut Venegoni, Chiara aut Lucianò, Roberta aut Gasparri, Anna Maria aut Colombo, Barbara aut Taiè, Giulia aut Jose, Jithin aut Armanetti, Paolo aut Menichetti, Luca aut Musco, Giovanna aut Salonia, Andrea aut Corti, Angelo (orcid)0000-0002-0893-6191 aut Curnis, Flavio (orcid)0000-0002-7231-9569 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 21(2023), 1 vom: 27. Aug. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:21 year:2023 number:1 day:27 month:08 https://dx.doi.org/10.1186/s12951-023-02028-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 27 08
allfields_unstemmed	10.1186/s12951-023-02028-5 doi (DE-627)SPR052890309 (SPR)s12951-023-02028-5-e DE-627 ger DE-627 rakwb eng Alfano, Massimo verfasserin aut A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract DGR motif (dpeaa)DE-He213 α5β1 integrin (dpeaa)DE-He213 Gold nanorods (dpeaa)DE-He213 Photoacoustic imaging (dpeaa)DE-He213 Bladder cancer (dpeaa)DE-He213 Alchera, Elisa aut Sacchi, Angelina aut Gori, Alessandro aut Quilici, Giacomo aut Locatelli, Irene aut Venegoni, Chiara aut Lucianò, Roberta aut Gasparri, Anna Maria aut Colombo, Barbara aut Taiè, Giulia aut Jose, Jithin aut Armanetti, Paolo aut Menichetti, Luca aut Musco, Giovanna aut Salonia, Andrea aut Corti, Angelo (orcid)0000-0002-0893-6191 aut Curnis, Flavio (orcid)0000-0002-7231-9569 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 21(2023), 1 vom: 27. Aug. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:21 year:2023 number:1 day:27 month:08 https://dx.doi.org/10.1186/s12951-023-02028-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 27 08
allfieldsGer	10.1186/s12951-023-02028-5 doi (DE-627)SPR052890309 (SPR)s12951-023-02028-5-e DE-627 ger DE-627 rakwb eng Alfano, Massimo verfasserin aut A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract DGR motif (dpeaa)DE-He213 α5β1 integrin (dpeaa)DE-He213 Gold nanorods (dpeaa)DE-He213 Photoacoustic imaging (dpeaa)DE-He213 Bladder cancer (dpeaa)DE-He213 Alchera, Elisa aut Sacchi, Angelina aut Gori, Alessandro aut Quilici, Giacomo aut Locatelli, Irene aut Venegoni, Chiara aut Lucianò, Roberta aut Gasparri, Anna Maria aut Colombo, Barbara aut Taiè, Giulia aut Jose, Jithin aut Armanetti, Paolo aut Menichetti, Luca aut Musco, Giovanna aut Salonia, Andrea aut Corti, Angelo (orcid)0000-0002-0893-6191 aut Curnis, Flavio (orcid)0000-0002-7231-9569 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 21(2023), 1 vom: 27. Aug. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:21 year:2023 number:1 day:27 month:08 https://dx.doi.org/10.1186/s12951-023-02028-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 27 08
allfieldsSound	10.1186/s12951-023-02028-5 doi (DE-627)SPR052890309 (SPR)s12951-023-02028-5-e DE-627 ger DE-627 rakwb eng Alfano, Massimo verfasserin aut A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract DGR motif (dpeaa)DE-He213 α5β1 integrin (dpeaa)DE-He213 Gold nanorods (dpeaa)DE-He213 Photoacoustic imaging (dpeaa)DE-He213 Bladder cancer (dpeaa)DE-He213 Alchera, Elisa aut Sacchi, Angelina aut Gori, Alessandro aut Quilici, Giacomo aut Locatelli, Irene aut Venegoni, Chiara aut Lucianò, Roberta aut Gasparri, Anna Maria aut Colombo, Barbara aut Taiè, Giulia aut Jose, Jithin aut Armanetti, Paolo aut Menichetti, Luca aut Musco, Giovanna aut Salonia, Andrea aut Corti, Angelo (orcid)0000-0002-0893-6191 aut Curnis, Flavio (orcid)0000-0002-7231-9569 aut Enthalten in Journal of nanobiotechnology London : Biomed Central, 2003 21(2023), 1 vom: 27. Aug. (DE-627)362770328 (DE-600)2100022-0 1477-3155 nnns volume:21 year:2023 number:1 day:27 month:08 https://dx.doi.org/10.1186/s12951-023-02028-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 27 08
language	English
source	Enthalten in Journal of nanobiotechnology 21(2023), 1 vom: 27. Aug. volume:21 year:2023 number:1 day:27 month:08
sourceStr	Enthalten in Journal of nanobiotechnology 21(2023), 1 vom: 27. Aug. volume:21 year:2023 number:1 day:27 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	DGR motif α5β1 integrin Gold nanorods Photoacoustic imaging Bladder cancer
isfreeaccess_bool	true
container_title	Journal of nanobiotechnology
authorswithroles_txt_mv	Alfano, Massimo @@aut@@ Alchera, Elisa @@aut@@ Sacchi, Angelina @@aut@@ Gori, Alessandro @@aut@@ Quilici, Giacomo @@aut@@ Locatelli, Irene @@aut@@ Venegoni, Chiara @@aut@@ Lucianò, Roberta @@aut@@ Gasparri, Anna Maria @@aut@@ Colombo, Barbara @@aut@@ Taiè, Giulia @@aut@@ Jose, Jithin @@aut@@ Armanetti, Paolo @@aut@@ Menichetti, Luca @@aut@@ Musco, Giovanna @@aut@@ Salonia, Andrea @@aut@@ Corti, Angelo @@aut@@ Curnis, Flavio @@aut@@
publishDateDaySort_date	2023-08-27T00:00:00Z
hierarchy_top_id	362770328
id	SPR052890309
language_de	englisch
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Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. 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author	Alfano, Massimo
spellingShingle	Alfano, Massimo misc DGR motif misc α5β1 integrin misc Gold nanorods misc Photoacoustic imaging misc Bladder cancer A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
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topic_title	A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods DGR motif (dpeaa)DE-He213 α5β1 integrin (dpeaa)DE-He213 Gold nanorods (dpeaa)DE-He213 Photoacoustic imaging (dpeaa)DE-He213 Bladder cancer (dpeaa)DE-He213
topic	misc DGR motif misc α5β1 integrin misc Gold nanorods misc Photoacoustic imaging misc Bladder cancer
topic_unstemmed	misc DGR motif misc α5β1 integrin misc Gold nanorods misc Photoacoustic imaging misc Bladder cancer
topic_browse	misc DGR motif misc α5β1 integrin misc Gold nanorods misc Photoacoustic imaging misc Bladder cancer
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title	A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
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title_full	A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
author_sort	Alfano, Massimo
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author_browse	Alfano, Massimo Alchera, Elisa Sacchi, Angelina Gori, Alessandro Quilici, Giacomo Locatelli, Irene Venegoni, Chiara Lucianò, Roberta Gasparri, Anna Maria Colombo, Barbara Taiè, Giulia Jose, Jithin Armanetti, Paolo Menichetti, Luca Musco, Giovanna Salonia, Andrea Corti, Angelo Curnis, Flavio
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author-letter	Alfano, Massimo
doi_str_mv	10.1186/s12951-023-02028-5
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title_sort	simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
title_auth	A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
abstract	Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract © The Author(s) 2023
abstractGer	Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract © The Author(s) 2023
abstract_unstemmed	Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. Results In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRsPEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism. Conclusion GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions. Graphical Abstract © The Author(s) 2023
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title_short	A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods
url	https://dx.doi.org/10.1186/s12951-023-02028-5
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author2	Alchera, Elisa Sacchi, Angelina Gori, Alessandro Quilici, Giacomo Locatelli, Irene Venegoni, Chiara Lucianò, Roberta Gasparri, Anna Maria Colombo, Barbara Taiè, Giulia Jose, Jithin Armanetti, Paolo Menichetti, Luca Musco, Giovanna Salonia, Andrea Corti, Angelo Curnis, Flavio
author2Str	Alchera, Elisa Sacchi, Angelina Gori, Alessandro Quilici, Giacomo Locatelli, Irene Venegoni, Chiara Lucianò, Roberta Gasparri, Anna Maria Colombo, Barbara Taiè, Giulia Jose, Jithin Armanetti, Paolo Menichetti, Luca Musco, Giovanna Salonia, Andrea Corti, Angelo Curnis, Flavio
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A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods

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