99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer

Paolo Rainone,1– 3 Antonella De Palma,4 Francesco Sudati,5 Valentina Roffia,4 Valentina Rigamonti,6 Lucia Salvioni,6 Miriam Colombo,6 Marilena Ripamonti,2 Antonello Enrico Spinelli,7 Davide Mazza,7 Pierluigi Mauri,4 Rosa Maria Moresco,1,2,7 Davide Prosperi,6 Sara Belloli2,7 1Department of...

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Autores principales:	Rainone P, De Palma A, Sudati F, Roffia V, Rigamonti V, Salvioni L, Colombo M, Ripamonti M, Spinelli AE, Mazza D, Mauri P, Moresco RM, Prosperi D, Belloli S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	her2-positive bc targeted silica nanoparticles tz-half chain conjugation 99mtc-radiolabeling spect imaging doxorubicin-loaded nanoparticles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b154f4bcc90247d2a2707ae5732b11ef
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id	oai:doaj.org-article:b154f4bcc90247d2a2707ae5732b11ef
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	her2-positive bc targeted silica nanoparticles tz-half chain conjugation 99mtc-radiolabeling spect imaging doxorubicin-loaded nanoparticles Medicine (General) R5-920
spellingShingle	her2-positive bc targeted silica nanoparticles tz-half chain conjugation 99mtc-radiolabeling spect imaging doxorubicin-loaded nanoparticles Medicine (General) R5-920 Rainone P De Palma A Sudati F Roffia V Rigamonti V Salvioni L Colombo M Ripamonti M Spinelli AE Mazza D Mauri P Moresco RM Prosperi D Belloli S 99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
description	Paolo Rainone,1– 3 Antonella De Palma,4 Francesco Sudati,5 Valentina Roffia,4 Valentina Rigamonti,6 Lucia Salvioni,6 Miriam Colombo,6 Marilena Ripamonti,2 Antonello Enrico Spinelli,7 Davide Mazza,7 Pierluigi Mauri,4 Rosa Maria Moresco,1,2,7 Davide Prosperi,6 Sara Belloli2,7 1Department of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy; 2Institute of Molecular Bioimaging and Physiology of CNR, Segrate, 20090, Italy; 3Doctorate School of Molecular and Translational Medicine, University of Milan, Milan, Italy; 4Institute of Biomedical Technologies of CNR, Segrate, 20090, Italy; 5PET and Nuclear Medicine Unit, San Raffaele Scientific Institute, Milan, 20132, Italy; 6NanoBioLab, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, 20126, Italy; 7Experimental Imaging Center, San Raffaele Scientific Institute, Milan, 20132, ItalyCorrespondence: Sara BelloliInstitute of Molecular Bioimaging and Physiology of CNR, Via Fratelli Cervi 93, Segrate, 20090, ItalyTel +39 02 26433640Fax +39 02 26432717Email belloli.sara@hsr.itIntroduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC.Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99mTc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors.Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls.Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.Keywords: HER2-positive BC, targeted silica nanoparticles, TZ-half chain conjugation, 99mTc-radiolabeling, SPECT imaging, doxorubicin-loaded nanoparticles
format	article
author	Rainone P De Palma A Sudati F Roffia V Rigamonti V Salvioni L Colombo M Ripamonti M Spinelli AE Mazza D Mauri P Moresco RM Prosperi D Belloli S
author_facet	Rainone P De Palma A Sudati F Roffia V Rigamonti V Salvioni L Colombo M Ripamonti M Spinelli AE Mazza D Mauri P Moresco RM Prosperi D Belloli S
author_sort	Rainone P
title	99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
title_short	99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
title_full	99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
title_fullStr	99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
title_full_unstemmed	99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer
title_sort	99mtc-radiolabeled silica nanocarriers for targeted detection and treatment of her2-positive breast cancer
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b154f4bcc90247d2a2707ae5732b11ef
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spelling	oai:doaj.org-article:b154f4bcc90247d2a2707ae5732b11ef2021-12-02T13:58:32Z99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer1178-2013https://doaj.org/article/b154f4bcc90247d2a2707ae5732b11ef2021-03-01T00:00:00Zhttps://www.dovepress.com/99mtc-radiolabeled-silica-nanocarriers-for-targeted-detection-and-trea-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Paolo Rainone,1– 3 Antonella De Palma,4 Francesco Sudati,5 Valentina Roffia,4 Valentina Rigamonti,6 Lucia Salvioni,6 Miriam Colombo,6 Marilena Ripamonti,2 Antonello Enrico Spinelli,7 Davide Mazza,7 Pierluigi Mauri,4 Rosa Maria Moresco,1,2,7 Davide Prosperi,6 Sara Belloli2,7 1Department of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy; 2Institute of Molecular Bioimaging and Physiology of CNR, Segrate, 20090, Italy; 3Doctorate School of Molecular and Translational Medicine, University of Milan, Milan, Italy; 4Institute of Biomedical Technologies of CNR, Segrate, 20090, Italy; 5PET and Nuclear Medicine Unit, San Raffaele Scientific Institute, Milan, 20132, Italy; 6NanoBioLab, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, 20126, Italy; 7Experimental Imaging Center, San Raffaele Scientific Institute, Milan, 20132, ItalyCorrespondence: Sara BelloliInstitute of Molecular Bioimaging and Physiology of CNR, Via Fratelli Cervi 93, Segrate, 20090, ItalyTel +39 02 26433640Fax +39 02 26432717Email belloli.sara@hsr.itIntroduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC.Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99mTc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors.Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls.Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.Keywords: HER2-positive BC, targeted silica nanoparticles, TZ-half chain conjugation, 99mTc-radiolabeling, SPECT imaging, doxorubicin-loaded nanoparticlesRainone PDe Palma ASudati FRoffia VRigamonti VSalvioni LColombo MRipamonti MSpinelli AEMazza DMauri PMoresco RMProsperi DBelloli SDove Medical Pressarticleher2-positive bctargeted silica nanoparticlestz-half chain conjugation99mtc-radiolabelingspect imagingdoxorubicin-loaded nanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1943-1960 (2021)

99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer

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