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2. Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.

Author

Wilson, Caroline L, Mann, Jelena, Walsh, Meagan, Perrugoria, Maria J, Oakley, Fiona, Wright, Matthew C, Brignole, Chiara, Di Paolo, Daniela, Perri, Patrizia, Ponzoni, Mirco, Karin, Michael, and Mann, Derek A

Subjects
Liver, Animals, Mice, Knockout, Mice, Rats, Sprague-Dawley, Interferons, Cytokines, Ligands, Cell Cycle, Transcription, Genetic, Toll-Like Receptor 3, Immunity, Innate, Hepatic Stellate Cells, Polycomb-Group Proteins, Immunity, Innate, Knockout, Rats, Sprague-Dawley, Transcription, Genetic, General Science & Technology
Abstract

Toll-like Receptor 3 (TLR3) is a pathogen pattern recognition receptor that plays a key role in innate immunity. TLR3 signalling has numerous functions in liver, both in health and disease. Here we report that TLR3 is expressed by quiescent hepatic stellate cells (HSC) where it functions to induce transcription and secretion of functional interferons as well as a number of other cytokines and chemokines. Upon transdifferentiation into myofibroblasts, HSCs rapidly loose the ability to produce interferon gamma (IFNγ). Mechanistically, this gene silencing may be due to Polycomb complex mediated repression via methylation of histone H3 lysine 27. In contrast to wild type, quiescent HSC isolated from tlr3 knockout mice do not produce IFNγ in response to Poly(I∶C) treatment. Therefore, quiescent HSC may contribute to induction of the hepatic innate immune system in response to injury or infection.

Published
2014

3. Supplementary Data from Enhanced Antitumor Efficacy of Clinical-Grade Vasculature-Targeted Liposomal Doxorubicin

Author

Pastorino, Fabio, primary, Di Paolo, Daniela, primary, Piccardi, Federica, primary, Nico, Beatrice, primary, Ribatti, Domenico, primary, Daga, Antonio, primary, Baio, Gabriella, primary, Neumaier, Carlo E., primary, Brignole, Chiara, primary, Loi, Monica, primary, Marimpietri, Danilo, primary, Pagnan, Gabriella, primary, Cilli, Michele, primary, Lepekhin, Eugene A., primary, Garde, Seema V., primary, Longhi, Renato, primary, Corti, Angelo, primary, Allen, Theresa M., primary, Wu, Jinzi J., primary, and Ponzoni, Mirco, primary

Published
2023
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4. Supplementary Data from The Combined Therapeutic Effects of Bortezomib and Fenretinide on Neuroblastoma Cells Involve Endoplasmic Reticulum Stress Response

Author

Pagnan, Gabriella, primary, Di Paolo, Daniela, primary, Carosio, Roberta, primary, Pastorino, Fabio, primary, Marimpietri, Danilo, primary, Brignole, Chiara, primary, Pezzolo, Annalisa, primary, Loi, Monica, primary, Galietta, Luis J.V., primary, Piccardi, Federica, primary, Cilli, Michele, primary, Nico, Beatrice, primary, Ribatti, Domenico, primary, Pistoia, Vito, primary, and Ponzoni, Mirco, primary

Published
2023
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5. Supplementary Figure S1 from Targeting Liposomal Chemotherapy via Both Tumor Cell–Specific and Tumor Vasculature–Specific Ligands Potentiates Therapeutic Efficacy

Author

Pastorino, Fabio, primary, Brignole, Chiara, primary, Di Paolo, Daniela, primary, Nico, Bice, primary, Pezzolo, Annalisa, primary, Marimpietri, Danilo, primary, Pagnan, Gabriella, primary, Piccardi, Federica, primary, Cilli, Michele, primary, Longhi, Renato, primary, Ribatti, Domenico, primary, Corti, Angelo, primary, Allen, Theresa M., primary, and Ponzoni, Mirco, primary

Published
2023
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6. Supplemental Figure 4 from The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, primary, Noghero, Alessio, primary, Murgia, Daniele, primary, Sementa, Angela R., primary, Cilli, Michele, primary, Pasqualini, Renata, primary, Arap, Wadih, primary, Bussolino, Federico, primary, Ponzoni, Mirco, primary, Pastorino, Fabio, primary, and Marchiò, Serena, primary

Published
2023
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7. Data from The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, primary, Noghero, Alessio, primary, Murgia, Daniele, primary, Sementa, Angela R., primary, Cilli, Michele, primary, Pasqualini, Renata, primary, Arap, Wadih, primary, Bussolino, Federico, primary, Ponzoni, Mirco, primary, Pastorino, Fabio, primary, and Marchiò, Serena, primary

Published
2023
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8. Supplemental Figure 2 from The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, primary, Noghero, Alessio, primary, Murgia, Daniele, primary, Sementa, Angela R., primary, Cilli, Michele, primary, Pasqualini, Renata, primary, Arap, Wadih, primary, Bussolino, Federico, primary, Ponzoni, Mirco, primary, Pastorino, Fabio, primary, and Marchiò, Serena, primary

Published
2023
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9. Supplementary Methods and Figure Legend from Targeting Liposomal Chemotherapy via Both Tumor Cell–Specific and Tumor Vasculature–Specific Ligands Potentiates Therapeutic Efficacy

Author

Pastorino, Fabio, primary, Brignole, Chiara, primary, Di Paolo, Daniela, primary, Nico, Bice, primary, Pezzolo, Annalisa, primary, Marimpietri, Danilo, primary, Pagnan, Gabriella, primary, Piccardi, Federica, primary, Cilli, Michele, primary, Longhi, Renato, primary, Ribatti, Domenico, primary, Corti, Angelo, primary, Allen, Theresa M., primary, and Ponzoni, Mirco, primary

Published
2023
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10. Supplemental Methods and Figure Legends from The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, primary, Noghero, Alessio, primary, Murgia, Daniele, primary, Sementa, Angela R., primary, Cilli, Michele, primary, Pasqualini, Renata, primary, Arap, Wadih, primary, Bussolino, Federico, primary, Ponzoni, Mirco, primary, Pastorino, Fabio, primary, and Marchiò, Serena, primary

Published
2023
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11. Supplemental Figure 3 from The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, primary, Noghero, Alessio, primary, Murgia, Daniele, primary, Sementa, Angela R., primary, Cilli, Michele, primary, Pasqualini, Renata, primary, Arap, Wadih, primary, Bussolino, Federico, primary, Ponzoni, Mirco, primary, Pastorino, Fabio, primary, and Marchiò, Serena, primary

Published
2023
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12. Supplemental Figure 1 from The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, primary, Noghero, Alessio, primary, Murgia, Daniele, primary, Sementa, Angela R., primary, Cilli, Michele, primary, Pasqualini, Renata, primary, Arap, Wadih, primary, Bussolino, Federico, primary, Ponzoni, Mirco, primary, Pastorino, Fabio, primary, and Marchiò, Serena, primary

Published
2023
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15. Novel phage display-derived neuroblastoma-targeting peptides potentiate the effect of drug nanocarriers in preclinical settings

Author

Loi, Monica, Di Paolo, Daniela, Soster, Marco, Brignole, Chiara, Bartolini, Alice, Emionite, Laura, Sun, Jessica, Becherini, Pamela, Curnis, Flavio, Petretto, Andrea, Sani, Monica, Gori, Alessandro, Milanese, Marco, Gambini, Claudio, Longhi, Renato, Cilli, Michele, Allen, Theresa M., Bussolino, Federico, Arap, Wadih, Pasqualini, Renata, Corti, Angelo, Ponzoni, Mirco, Marchiò, Serena, and Pastorino, Fabio

Published
2013
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16. MiR-486-5p Targets CD133+ Lung Cancer Stem Cells through the p85/AKT Pathway

Author

Moro, Massimo, primary, Fortunato, Orazio, additional, Bertolini, Giulia, additional, Mensah, Mavis, additional, Borzi, Cristina, additional, Centonze, Giovanni, additional, Andriani, Francesca, additional, Di Paolo, Daniela, additional, Perri, Patrizia, additional, Ponzoni, Mirco, additional, Pastorino, Ugo, additional, Sozzi, Gabriella, additional, and Boeri, Mattia, additional

Published
2022
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17. Combined targeting of perivascular and endothelial tumor cells enhances anti-tumor efficacy of liposomal chemotherapy in neuroblastoma

Author

Loi, Monica, Marchiò, Serena, Becherini, Pamela, Di Paolo, Daniela, Soster, Marco, Curnis, Flavio, Brignole, Chiara, Pagnan, Gabriella, Perri, Patrizia, Caffa, Irene, Longhi, Renato, Nico, Beatrice, Bussolino, Federico, Gambini, Claudio, Ribatti, Domenico, Cilli, Michele, Arap, Wadih, Pasqualini, Renata, Allen, Theresa M., Corti, Angelo, Ponzoni, Mirco, and Pastorino, Fabio

Published
2010
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20. Cotargeting of miR‐126‐3p and miR‐221‐3p inhibits PIK3R2 and PTEN, reducing lung cancer growth and metastasis by blocking AKT and CXCR4 signalling

Author

Di Paolo, Daniela, primary, Pontis, Francesca, additional, Moro, Massimo, additional, Centonze, Giovanni, additional, Bertolini, Giulia, additional, Milione, Massimo, additional, Mensah, Mavis, additional, Segale, Miriam, additional, Petraroia, Ilaria, additional, Borzi, Cristina, additional, Suatoni, Paola, additional, Brignole, Chiara, additional, Perri, Patrizia, additional, Ponzoni, Mirco, additional, Pastorino, Ugo, additional, Sozzi, Gabriella, additional, and Fortunato, Orazio, additional

Published
2021
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21. Chapter 12 Liposome-Mediated Therapy of Neuroblastoma

Author

Di Paolo, Daniela, primary, Loi, Monica, additional, Pastorino, Fabio, additional, Brignole, Chiara, additional, Marimpietri, Danilo, additional, Becherini, Pamela, additional, Caffa, Irene, additional, Zorzoli, Alessia, additional, Longhi, Renato, additional, Gagliani, Cristina, additional, Tacchetti, Carlo, additional, Corti, Angelo, additional, Allen, Theresa M., additional, Ponzoni, Mirco, additional, and Pagnan, Gabriella, additional

Published
2009
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22. Combined Replenishment of miR‐34a and let‐7b by Targeted Nanoparticles Inhibits Tumor Growth in Neuroblastoma Preclinical Models

Author

Di Paolo, Daniela, primary, Pastorino, Fabio, additional, Brignole, Chiara, additional, Corrias, Maria Valeria, additional, Emionite, Laura, additional, Cilli, Michele, additional, Tamma, Roberto, additional, Priddy, Leslie, additional, Amaro, Adriana, additional, Ferrari, Davide, additional, Marotta, Roberto, additional, Ferretti, Elisa, additional, Pfeffer, Ulrich, additional, Ribatti, Domenico, additional, Sementa, Angela Rita, additional, Brown, David, additional, Ikegaki, Naohiko, additional, Shimada, Hiroyuki, additional, Ponzoni, Mirco, additional, and Perri, Patrizia, additional

Published
2020
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23. A Proof-of-Concept for Epigenetic Therapy of Tissue Fibrosis: Inhibition of Liver Fibrosis Progression by 3-Deazaneplanocin A

Author

Zeybel, Müjdat, Luli, Saimir, Sabater, Laura, Hardy, Timothy, Oakley, Fiona, Leslie, Jack, Page, Agata, Moran Salvador, Eva, Sharkey, Victoria, Tsukamoto, Hidekazu, Chu, David C.K., Singh, Uma Sharan, Ponzoni, Mirco, Perri, Patrizia, Di Paolo, Daniela, Mendivil, Edgar J., Mann, Jelena, and Mann, Derek A.

Subjects
Liver Cirrhosis, Male, Adenosine, Collagen Type I, Epigenesis, Genetic, Histones, Mice, Drug Discovery, Hepatic Stellate Cells, Genetics, Animals, EZH2, Myofibroblasts, Carbon Tetrachloride, Molecular Biology, liver fibrosis, Pharmacology, Gene Expression Profiling, Histone-Lysine N-Methyltransferase, 3-deazaneplanocin A, Disease Models, Animal, Gene Expression Regulation, Disease Progression, Histone Methyltransferases, Molecular Medicine, Original Article, epigenetic, Biomarkers
Abstract

The progression of fibrosis in chronic liver disease is dependent upon hepatic stellate cells (HSCs) transdifferentiating to a myofibroblast-like phenotype. This pivotal process is controlled by enzymes that regulate histone methylation and chromatin structure, which may be targets for developing anti-fibrotics. There is limited pre-clinical experimental support for the potential to therapeutically manipulate epigenetic regulators in fibrosis. In order to learn if epigenetic treatment can halt the progression of pre-established liver fibrosis, we treated mice with the histone methyltransferase inhibitor 3-deazaneplanocin A (DZNep) in a naked form or by selectively targeting HSC-derived myofibroblasts via an antibody-liposome-DZNep targeting vehicle. We discovered that DZNep treatment inhibited multiple histone methylation modifications, indicative of a broader specificity than previously reported. This broad epigenetic repression was associated with the suppression of fibrosis progression as assessed both histologically and biochemically. The anti-fibrotic effect of DZNep was reproduced when the drug was selectively targeted to HSC-derived myofibroblasts. Therefore, the in vivo modulation of HSC histone methylation is sufficient to halt progression of fibrosis in the context of continuous liver damage. This discovery and our novel HSC-targeting vehicle, which avoids the unwanted effects of epigenetic drugs on parenchymal liver cells, represents an important proof-of-concept for epigenetic treatment of liver fibrosis., Fibrosis results in progressive deposition of scar tissue leading to cirrhosis. The histone methyltransferase EZH2 regulates the activity of scar-forming myofibroblasts. By developing a liposome vehicle decorated with an antibody selective for myofibroblasts, we demonstrate that in vivo pharmacological targeting of myofibroblast EZH2 is sufficient to block fibrosis progression in chronic liver disease.

Published
2017
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26. The Depolarization-Evoked, Ca2+-Dependent Release of Exosomes From Mouse Cortical Nerve Endings: New Insights Into Synaptic Transmission.

Author

Olivero, Guendalina, Cisani, Francesca, Marimpietri, Danilo, Di Paolo, Daniela, Gagliani, Maria Cristina, Podestà, Marina, Cortese, Katia, and Pittaluga, Anna

Subjects
EXOSOMES, NERVE endings, NEURAL transmission, EXTRACELLULAR vesicles, PRESYNAPTIC receptors, TRANSMISSION electron microscopy, SYNAPTOSOMES, LIGHT scattering
Abstract

Whether exosomes can be actively released from presynaptic nerve terminals is a matter of debate. To address the point, mouse cortical synaptosomes were incubated under basal and depolarizing (25 mM KCl-enriched medium) conditions, and extracellular vesicles were isolated from the synaptosomal supernatants to be characterized by dynamic light scattering, transmission electron microscopy, Western blot, and flow cytometry analyses. The structural and biochemical analysis unveiled that supernatants contain vesicles that have the size and the shape of exosomes, which were immunopositive for the exosomal markers TSG101, flotillin-1, CD63, and CD9. The marker content increased upon the exposure of nerve terminals to the high-KCl stimulus, consistent with an active release of the exosomes from the depolarized synaptosomes. High KCl-induced depolarization elicits the Ca2+-dependent exocytosis of glutamate. Interestingly, the depolarization-evoked release of exosomes from cortical synaptosomes also occurred in a Ca2+-dependent fashion, since the TSG101, CD63, and CD9 contents in the exosomal fraction isolated from supernatants of depolarized synaptosomes were significantly reduced when omitting external Ca2+ ions. Differently, (±)-baclofen (10 µM), which significantly reduced the glutamate exocytosis, did not affect the amount of exosomal markers, suggesting that the GABAB-mediated mechanism does not control the exosome release. Our findings suggest that the exposure of synaptosomes to a depolarizing stimulus elicits a presynaptic release of exosomes that occurs in a Ca2+-dependent fashion. The insensitivity to the presynaptic GABAB receptors, however, leaves open the question on whether the release of exosomes could be a druggable target for new therapeutic intervention for the cure of synaptopathies. [ABSTRACT FROM AUTHOR]

Published
2021
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28. Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles

Author

Ponzoni, Mirco, primary, Curnis, Flavio, additional, Brignole, Chiara, additional, Bruno, Silvia, additional, Guarnieri, Daniela, additional, Sitia, Leopoldo, additional, Marotta, Roberto, additional, Sacchi, Angelina, additional, Bauckneht, Matteo, additional, Buschiazzo, Ambra, additional, Rossi, Andrea, additional, Di Paolo, Daniela, additional, Perri, Patrizia, additional, Gori, Alessandro, additional, Sementa, Angela R., additional, Emionite, Laura, additional, Cilli, Michele, additional, Tamma, Roberto, additional, Ribatti, Domenico, additional, Pompa, Pier Paolo, additional, Marini, Cecilia, additional, Sambuceti, Gianmario, additional, Corti, Angelo, additional, and Pastorino, Fabio, additional

Published
2018
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30. Abstract 3844: A novel liposomal Clodronate depletes tumor-associated macrophages in primary and metastatic melanoma: anti-angiogenic and anti-tumor effects

Author

Brignole, Chiara, primary, Perri, Patrizia, additional, Piaggio, Francesca, additional, Pastorino, Fabio, additional, Di Paolo, Daniela, additional, Emionite, Laura, additional, Daga, Antonio, additional, Kondylis, Vangelis, additional, Pasparakis, Manolis, additional, Ribatti, Domenico, additional, and Ponzoni, Mirco, additional

Published
2016
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31. A new fluorescence-based optical imaging method to non-invasively monitor hepatic myofibroblasts in vivo

Author

Luli, Saimir, primary, Di Paolo, Daniela, additional, Perri, Patrizia, additional, Brignole, Chiara, additional, Hill, Stephen J., additional, Brown, Helen, additional, Leslie, Jack, additional, Marshall, H.L., additional, Wright, Matthew C., additional, Mann, Derek A., additional, Ponzoni, Mirco, additional, and Oakley, Fiona, additional

Published
2016
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32. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion

Author

Cossu, Irene, primary, Bottoni, Gianluca, additional, Loi, Monica, additional, Emionite, Laura, additional, Bartolini, Alice, additional, Di Paolo, Daniela, additional, Brignole, Chiara, additional, Piaggio, Francesca, additional, Perri, Patrizia, additional, Sacchi, Angelina, additional, Curnis, Flavio, additional, Gagliani, Maria Cristina, additional, Bruno, Silvia, additional, Marini, Cecilia, additional, Gori, Alessandro, additional, Longhi, Renato, additional, Murgia, Daniele, additional, Sementa, Angela Rita, additional, Cilli, Michele, additional, Tacchetti, Carlo, additional, Corti, Angelo, additional, Sambuceti, Gianmario, additional, Marchiò, Serena, additional, Ponzoni, Mirco, additional, and Pastorino, Fabio, additional

Published
2015
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33. The Neuronal Pentraxin-2 Pathway Is an Unrecognized Target in Human Neuroblastoma, Which Also Offers Prognostic Value in Patients

Author

Bartolini, Alice, primary, Di Paolo, Daniela, additional, Noghero, Alessio, additional, Murgia, Daniele, additional, Sementa, Angela R., additional, Cilli, Michele, additional, Pasqualini, Renata, additional, Arap, Wadih, additional, Bussolino, Federico, additional, Ponzoni, Mirco, additional, Pastorino, Fabio, additional, and Marchiò, Serena, additional

Published
2015
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34. New therapeutic strategies in neuroblastoma: combined targeting of a novel tyrosine kinase inhibitor and liposomal siRNAs against ALK

Author

Di Paolo, Daniela, primary, Yang, D., additional, Pastorino, Fabio, additional, Emionite, Laura, additional, Cilli, Michele, additional, Daga, Antonio, additional, Destafanis, Elisa, additional, Di Fiore, Annarita, additional, Piaggio, Francesca, additional, Brignole, Chiara, additional, Xu, Xiaobao, additional, Liang, Chris, additional, Gibbons, James, additional, Ponzoni, Mirco, additional, and Perri, Patrizia, additional

Published
2015
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35. Abstract 5620: Novel phage display-derived neuroblastoma-targeting peptides potentiate the effect of drug nanocarriers in preclinical settings.

Author

Loi, Monica, primary, Di Paolo, Daniela, additional, Soster, Marco, additional, Brignole, Chiara, additional, Bartolini, Alice, additional, Emionite, Laura, additional, Sun, Jessica, additional, Becherini, Pamela, additional, Curnis, Flavio, additional, Petretto, Andrea, additional, Sani, Monica, additional, Gori, Alessandro, additional, Gambini, Claudio, additional, Longhi, Renato, additional, Cilli, Michele, additional, Allen, Theresa M., additional, Bussolino, Federico, additional, Arap, Wadih, additional, Pasqualini, Renata, additional, Corti, Angelo, additional, Ponzoni, Mirco, additional, Marchiò, Serena, additional, and Pastorino, Fabio, additional

Published
2013
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37. Selective Therapeutic Targeting of the Anaplastic Lymphoma Kinase With Liposomal siRNA Induces Apoptosis and Inhibits Angiogenesis in Neuroblastoma

Author

Di Paolo, Daniela, primary, Ambrogio, Chiara, additional, Pastorino, Fabio, additional, Brignole, Chiara, additional, Martinengo, Cinzia, additional, Carosio, Roberta, additional, Loi, Monica, additional, Pagnan, Gabriella, additional, Emionite, Laura, additional, Cilli, Michele, additional, Ribatti, Domenico, additional, Allen, Theresa M, additional, Chiarle, Roberto, additional, Ponzoni, Mirco, additional, and Perri, Patrizia, additional

Published
2011
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38. Neuroblastoma-targeted Nanoparticles Entrapping siRNA Specifically Knockdown ALK

Author

Di Paolo, Daniela, primary, Brignole, Chiara, additional, Pastorino, Fabio, additional, Carosio, Roberta, additional, Zorzoli, Alessia, additional, Rossi, Marzia, additional, Loi, Monica, additional, Pagnan, Gabriella, additional, Emionite, Laura, additional, Cilli, Michele, additional, Bruno, Silvia, additional, Chiarle, Roberto, additional, Allen, Theresa M, additional, Ponzoni, Mirco, additional, and Perri, Patrizia, additional

Published
2011
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39. The use of the orthotopic model to validate antivascular therapies for cancer

Author

Loi, Monica, primary, Di Paolo, Daniela, additional, Becherini, Pamela, additional, Zorzoli, Alessia, additional, Perri, Patrizia, additional, Carosio, Roberta, additional, Cilli, Michele, additional, Ribatti, Domenico, additional, Brignole, Chiara, additional, Pagnan, Gabriella, additional, Ponzoni, Mirco, additional, and Pastorino, Fabio, additional

Published
2011
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40. PHOX2B-Mediated Regulation of ALK Expression: In Vitro Identification of a Functional Relationship between Two Genes Involved in Neuroblastoma

Author

Bachetti, Tiziana, primary, Di Paolo, Daniela, additional, Di Lascio, Simona, additional, Mirisola, Valentina, additional, Brignole, Chiara, additional, Bellotti, Marta, additional, Caffa, Irene, additional, Ferraris, Chiara, additional, Fiore, Michele, additional, Fornasari, Diego, additional, Chiarle, Roberto, additional, Borghini, Silvia, additional, Pfeffer, Ulrich, additional, Ponzoni, Mirco, additional, Ceccherini, Isabella, additional, and Perri, Patrizia, additional

Published
2010
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41. Abstract A130: Effects of a novel liposomal formulation of fenretinide on human neuroblastoma cell growth, apoptosis and angiogenesis

Author

Di Paolo, Daniela, primary, Caffa, Irene, additional, Pastorino, Fabio, additional, Loi, Monica, additional, Marimpietri, Danilo, additional, Brignole, Chiara, additional, Perri, Patrizia, additional, Cilli, Michele, additional, Nico, Beatrice, additional, Ribatti, Domenico, additional, Ponzoni, Mirco, additional, and Pagnan, Gabriella, additional

Published
2009
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42. The Combined Therapeutic Effects of Bortezomib and Fenretinide on Neuroblastoma Cells Involve Endoplasmic Reticulum Stress Response

Author

Pagnan, Gabriella, primary, Di Paolo, Daniela, additional, Carosio, Roberta, additional, Pastorino, Fabio, additional, Marimpietri, Danilo, additional, Brignole, Chiara, additional, Pezzolo, Annalisa, additional, Loi, Monica, additional, Galietta, Luis J.V., additional, Piccardi, Federica, additional, Cilli, Michele, additional, Nico, Beatrice, additional, Ribatti, Domenico, additional, Pistoia, Vito, additional, and Ponzoni, Mirco, additional

Published
2009
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43. Enhanced Antitumor Efficacy of Clinical-Grade Vasculature-Targeted Liposomal Doxorubicin

Author

Pastorino, Fabio, primary, Di Paolo, Daniela, additional, Piccardi, Federica, additional, Nico, Beatrice, additional, Ribatti, Domenico, additional, Daga, Antonio, additional, Baio, Gabriella, additional, Neumaier, Carlo E., additional, Brignole, Chiara, additional, Loi, Monica, additional, Marimpietri, Danilo, additional, Pagnan, Gabriella, additional, Cilli, Michele, additional, Lepekhin, Eugene A., additional, Garde, Seema V., additional, Longhi, Renato, additional, Corti, Angelo, additional, Allen, Theresa M., additional, Wu, Jinzi J., additional, and Ponzoni, Mirco, additional

Published
2008
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45. Combined Therapeutic Effects of Vinblastine and Rapamycin on Human Neuroblastoma Growth, Apoptosis, and Angiogenesis

Author

Marimpietri, Danilo, primary, Brignole, Chiara, additional, Nico, Beatrice, additional, Pastorino, Fabio, additional, Pezzolo, Annalisa, additional, Piccardi, Federica, additional, Cilli, Michele, additional, Di Paolo, Daniela, additional, Pagnan, Gabriella, additional, Longo, Luca, additional, Perri, Patrizia, additional, Ribatti, Domenico, additional, and Ponzoni, Mirco, additional

Published
2007
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46. Targeting Liposomal Chemotherapy via Both Tumor Cell–Specific and Tumor Vasculature–Specific Ligands Potentiates Therapeutic Efficacy

Author

Pastorino, Fabio, primary, Brignole, Chiara, additional, Di Paolo, Daniela, additional, Nico, Bice, additional, Pezzolo, Annalisa, additional, Marimpietri, Danilo, additional, Pagnan, Gabriella, additional, Piccardi, Federica, additional, Cilli, Michele, additional, Longhi, Renato, additional, Ribatti, Domenico, additional, Corti, Angelo, additional, Allen, Theresa M., additional, and Ponzoni, Mirco, additional

Published
2006
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47. A new fluorescence-based optical imaging method to non-invasively monitor hepatic myofibroblasts in vivo

Author

Luli, Saimir, Di Paolo, Daniela, Perri, Patrizia, Brignole, Chiara, Hill, Stephen J., Brown, Helen, Leslie, Jack, Marshall, H.L., Wright, Matthew C., Mann, Derek A., Ponzoni, Mirco, and Oakley, Fiona

Subjects
Hepatic myofibroblasts, Hepatology, Mouse, Non-invasive imaging, Cell-targeting, Fibrosis
Abstract

Background & AimsCurrently, staging of fibrosis in preclinical rodent liver fibrosis models is achieved histologically. Many animals are used at multiple time-points to assess disease progression or therapeutic responses. Hepatic myofibroblasts promote liver fibrosis therefore quantifying these cells in vivo could assess disease or predict therapeutic responses in mice. We fluorescently labelled a single chain antibody (C1-3) that binds hepatic myofibroblasts to monitor fibrogenesis in vivo.MethodsCCl4 was used to induce acute liver injury in WT and cRel−/− mice. Bile duct ligation was used to model chronic fibrosis. Hepatic myofibroblasts were depleted using a liposome-drug delivery system or chemically with sulfasalazine. An IVIS® spectrum visualised fluorophore-conjugated C1-3 in vivo.ResultsIVIS detection of fluorescently labelled-C1-3 but not a control antibody discriminates between fibrotic and non-fibrotic liver in acute and chronic liver fibrosis models. cRel−/− mice have a fibro-protective phenotype and IVIS signal is reduced in CCl4 injured cRel−/− mice compared to wild-type. In vivo imaging of fluorescently labelled-C1-3 successfully predicts reductions in hepatic myofibroblast numbers in fibrotic liver disease in response to therapy.ConclusionsWe report a novel fluorescence imaging method to assess murine hepatic myofibroblast numbers in vivo during liver fibrosis and after therapy. We also describe a novel liposomal antibody targeting system to selectively deliver drugs to hepatic myofibroblasts in vivo. C1-3 binds human hepatic myofibroblast therefore imaging labelled-C1-3 could be used for clinical studies in man to help stage fibrosis, demonstrate efficacy of drugs that promote hepatic myofibroblast clearance or predict early therapeutic responses.Lay summaryIn response to damage and injury scars develop in the liver and the main cell that makes the scar tissue is the hepatic myofibroblast (HM). C1-3 is an antibody fragment that binds to the scar forming HM. We have fluorescently labelled C1-3 and given it to mice that have either normal or scarred livers (which contain HM) and then used a machine called an in vivo imaging system (IVIS) that takes pictures of different wavelengths of light, to visualise the antibody binding to HM inside the living mouse. Using fluorescently labelled C1-3 we can assess HM numbers in the injured liver and monitor response to therapy. We have also used C1-3 to target drugs encapsulated in lipid carriers (liposomes) to the HM to kill the HM and reduce the liver disease.

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49. Overcoming Biological Barriers in Neuroblastoma Therapy: The Vascular Targeting Approach with Liposomal Drug Nanocarriers

Author

Mirco Ponzoni, Daniela Di Paolo, Patrizia Perri, Angelo Corti, Chiara Brignole, Flavio Curnis, Fabio Pastorino, Pastorino, Fabio, Brignole, Chiara, Di Paolo, Daniela, Perri, Patrizia, Curnis, Flavio, Corti, Angelo, and Ponzoni, Mirco

Subjects
Drug, Fenretinide, Angiogenesis, medicine.medical_treatment, media_common.quotation_subject, Antineoplastic Agents, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Targeted therapy, Biomaterials, Bortezomib, neuroblastoma, Neuroblastoma, Drug Delivery Systems, Medicine, Animals, Humans, General Materials Science, media_common, business.industry, Chemistry (all), General Chemistry, targeted therapy, 021001 nanoscience & nanotechnology, medicine.disease, Biomaterial, Pediatric cancer, 0104 chemical sciences, tumor vascular targeting, Targeted drug delivery, Doxorubicin, drug delivery, liposome, Drug delivery, Liposomes, Cancer research, Materials Science (all), Nanocarriers, 0210 nano-technology, business, Biotechnology
Abstract

Neuroblastoma is a rare pediatric cancer characterized by a wide clinical behavior and adverse outcome despite aggressive therapies. New approaches based on targeted drug delivery may improve efficacy and decrease toxicity of cancer therapy. Furthermore, nanotechnology offers additional potential developments for cancer imaging, diagnosis, and treatment. Following these lines, in the past years, innovative therapies based on the use of liposomes loaded with anticancer agents and functionalized with peptides capable of recognizing neuroblastoma cells and/or tumor-associated endothelial cells have been developed. Studies performed in experimental orthotopic models of human neuroblastoma have shown that targeted nanocarriers can be exploited for not only decreasing the systemic toxicity of the encapsulated anticancer drugs, but also increasing their tumor homing properties, enhancing tumor vascular permeability and perfusion (and, consequently, drug penetration), inducing tumor apoptosis, inhibiting angiogenesis, and reducing tumor glucose consumption. Furthermore, peptide-tagged liposomal formulations are proved to be more efficacious in inhibiting tumor growth and metastatic spreading of neuroblastoma than nontargeted liposomes. These findings, herein reviewed, pave the way for the design of novel targeted liposomal nanocarriers useful for multitargeting treatment of neuroblastoma.

Published
2018

50. Enhancement of Tumor Homing by Chemotherapy-Loaded Nanoparticles

Author

Roberto Tamma, Laura Emionite, Patrizia Perri, Daniela Guarnieri, Pier Paolo Pompa, Angelina Sacchi, Mirco Ponzoni, Daniela Di Paolo, Cecilia Marini, Angelo Corti, Silvia Bruno, Flavio Curnis, Leopoldo Sitia, Chiara Brignole, Ambra Buschiazzo, Matteo Bauckneht, Alessandro Gori, Michele Cilli, Roberto Marotta, Domenico Ribatti, Gianmario Sambuceti, Angela Rita Sementa, Andrea Rossi, Fabio Pastorino, Ponzoni, Mirco, Curnis, Flavio, Brignole, Chiara, Bruno, Silvia, Guarnieri, Daniela, Sitia, Leopoldo, Marotta, Roberto, Sacchi, Angelina, Bauckneht, Matteo, Buschiazzo, Ambra, Rossi, Andrea, Di Paolo, Daniela, Perri, Patrizia, Gori, Alessandro, Sementa, Angela R., Emionite, Laura, Cilli, Michele, Tamma, Roberto, Ribatti, Domenico, Pompa, Pier Paolo, Marini, Cecilia, Sambuceti, Gianmario, Corti, Angelo, and Pastorino, Fabio

Subjects
0301 basic medicine, education, Antineoplastic Agents, Polyethylene Glycols, Biomaterials, Neuroblastoma, 03 medical and health sciences, neuroblastoma, Drug Delivery Systems, 0302 clinical medicine, In vivo, tumor penetration, Cell Line, Tumor, medicine, Animals, Humans, General Materials Science, Doxorubicin, Drug delivery, nanoparticles, targeted therapy, Chemistry, nanoparticle, Chemistry (all), drug delivery, Biotechnology, Materials Science (all), General Chemistry, medicine.disease, Xenograft Model Antitumor Assays, Biomaterial, Neuropilin-1, In vitro, 030104 developmental biology, Cell culture, 030220 oncology & carcinogenesis, cardiovascular system, Cancer research, Nanoparticles, Nanocarriers, circulatory and respiratory physiology, Homing (hematopoietic), medicine.drug
Abstract

Targeted delivery of anticancer drugs with nanocarriers can reduce side effects and ameliorate therapeutic efficacy. However, poorly perfused and dysfunctional tumor vessels limit the transport of the payload into solid tumors. The use of tumor-penetrating nanocarriers might enhance tumor uptake and antitumor effects. A peptide containing a tissue-penetrating (TP) consensus motif, capable of recognizing neuropilin-1, is here fused to a neuroblastoma-targeting peptide (pep) previously developed. Neuroblastoma cell lines and cells derived from both xenografts and high-risk neuroblastoma patients show overexpression of neuropilin-1. In vitro studies reveal that TP-pep binds cell lines and cells derived from neuroblastoma patients more efficiently than pep. TP-pep, after coupling to doxorubicin-containing stealth liposomes (TP-pep-SL[doxorubicin]), enhances their uptake by cells and cytotoxic effects in vitro, while increasing tumor-binding capability and homing in vivo. TP-pep-SL[doxorubicin] treatment enhances the Evans Blue dye accumulation in tumors but not in nontumor tissues, pointing to selective increase of vascular permeability in tumor tissues. Compared to pep-SL[doxorubicin], TP-pep-SL[doxorubicin] shows an increased antineuroblastoma activity in three neuroblastoma animal models mimicking the growth of neuroblastoma in humans. The enhancement of drug penetration in tumors by TP-pep-targeted nanoparticles may represent an innovative strategy for neuroblastoma.

Published
2018

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