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3. CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells

Author

Goodwin, M, Lee, E, Lakshmanan, U, Shipp, S, Froessl, L, Barzaghi, F, Passerini, L, Narula, M, Sheikali, A, Lee, CM, Bao, G, Bauer, CS, Miller, HK, Garcia-Lloret, M, Butte, MJ, Bertaina, A, Shah, A, Pavel-Dinu, M, Hendel, A, Porteus, M, Roncarolo, MG, and Bacchetta, R

Subjects
Genetics, Biotechnology, Rare Diseases, Stem Cell Research, Autoimmune Disease, Regenerative Medicine, Pediatric, Aetiology, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Child, Forkhead Transcription Factors, Gene Editing, Genetic Diseases, X-Linked, Humans, Mutation, Phenotype, T-Lymphocytes, Regulatory
Abstract

The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.

Published
2020

6. Hematopoietic Stem/Progenitor Cells and Engineering: T-ALLO10 INFUSION AFTER AβDEPLETED-HSCT IN CHILDREN AND YOUNG ADULTS WITH HEMATOLOGIC MALIGNANCIES: IMPROVED IMMUNE RECONSTITUTION IN THE ABSENCE OF SEVERE GVHD

Author

Bertaina, A., primary, Bacchetta, R., additional, Shyr, D.C., additional, Saini, G., additional, Lee, J., additional, Kristovich, K., additional, Agarwal, R., additional, Klein, O., additional, Melsop, K., additional, Tate, K., additional, Barbarito, G., additional, Oppizzi, L., additional, Chen, P., additional, Cepika, A., additional, and Roncarolo, M., additional

Published
2023
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8. Gene Editing/Gene Therapies: BENCH TO BEDSIDE: ENGINEERED AUTOLOGOUS CD4LVFOXP3 TREG-LIKE CELL PRODUCT FOR PHASE 1 STUDY IN PATIENTS WITH IPEX SYNDROME

Author

Nathan, A., primary, Sato, Y., additional, Tate, K., additional, wani, P., additional, Terry, C., additional, Fazeli, F., additional, Bouge, A., additional, Goodwin, E., additional, Wright, J., additional, Bertaina, A., additional, Klein, O., additional, Agarwal, R., additional, Roncarolo, M., additional, and Bacchetta, R., additional

Published
2022
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10. Contributors

Author

Agua-Doce, A., primary, Awe, O., additional, Azevedo, R.I., additional, Bacchetta, R., additional, Bortell, R., additional, Brehm, M.A., additional, Burska, A.N., additional, Csomos, K., additional, Denny, J.C., additional, Dudley, J.T., additional, Farmer, J., additional, Getts, D.R., additional, Graca, L., additional, Greiner, D.L., additional, Harrison, S.R., additional, Hillion, S., additional, Kaplan, M.H., additional, Kidd, B.A., additional, Lacerda, J.F., additional, Lee, Y.N., additional, Miller, S.D., additional, Monteiro, M., additional, Ponchel, F., additional, Shultz, L.D., additional, Simon, Q., additional, Smarr, C.B., additional, Ueno, H., additional, Verma, M., additional, Walter, J.E., additional, Warner, J.L., additional, and Yang, Jianfei, additional

Published
2016
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19. Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study

Author

Barzaghi, F., Hernandez, L.C.A., Neven, B., Ricci, S., Kucuk, Z.Y., Bleesing, J.J., Nademi, Z., Slatter, M.A., Ulloa, E.R., Shcherbina, A., Roppelt, A., Worth, A., Silva, J., Aiuti, A., Murguia-Favela, L., Speckmann, C., Carneiro-Sampaio, M., Fernandes, J.F., Baris, S., Ozen, A., Karakoc-Aydiner, E., Kiykim, A., Schulz, A., Steinmann, S., Notarangelo, L.D., Gambineri, E., Lionetti, P., Shearer, W.T., Forbes, L.R., Martinez, C., Moshous, D., Blanche, S., Fisher, A., Ruemmele, F.M., Tissandier, C., Ouachee-Chardin, M., Rieux-Laucat, F., Cavazzana, M., Qasim, W., Lucarelli, B., Albert, M.H., Kobayashi, I., Alonso, L., Heredia, C.D. de, Kanegane, H., Lawitschka, A., Seo, J.J., Gonzalez-Vicent, M., Diaz, M.A., Goyal, R.K., Sauer, M.G., Yesilipek, A., Kim, M., Yilmaz-Demirdag, Y., Bhatia, M., Khlevner, J., Padilla, E.J.R., Martino, S., Montin, D., Neth, O., Molinos-Quintana, A., Valverde-Fernandez, J., Broides, A., Pinsk, V., Ballauf, A., Haerynck, F., Bordon, V., Dhooge, C., Garcia-Lloret, M.L., Bredius, R.G., Kawak, K., Haddad, E., Seidel, M.G., Duckers, G., Pai, S.Y., Dvorak, C.C., Ehl, S., Locatelli, F., Goldman, F., Gennery, A.R., Cowan, M.J., Roncarolo, M.G., Bacchetta, R., PIDTC, IEWP, European Soc Blood Marrow, Barzaghi, Federica, Hernandez, Laura Cristina Amaya, Neven, Benedicte, Ricci, Silvia, Kucuk, Zeynep Yesim, Bleesing, Jack J., Nademi, Zohreh, Slatter, Mary Anne, Ulloa, Erlinda Rose, Shcherbina, Anna, Roppelt, Anna, Worth, Austen, Silva, Juliana, Aiuti, Alessandro, Murguia-Favela, Luis, Speckmann, Carsten, Carneiro-Sampaio, Magda, Fernandes, Juliana Folloni, Baris, Safa, Ozen, Ahmet, Karakoc-Aydiner, Elif, Kiykim, Ayca, Schulz, Ansgar, Steinmann, Sandra, Notarangelo, Lucia Dora, Gambineri, Eleonora, Lionetti, Paolo, Shearer, William Thomas, Forbes, Lisa R., Martinez, Caridad, Moshous, Despina, Blanche, Stephane, Fisher, Alain, Ruemmele, Frank M., Tissandier, Come, Ouachee-Chardin, Marie, Rieux-Laucat, Frederic, Cavazzana, Marina, Qasim, Waseem, Lucarelli, Barbarella, Albert, Michael H., Kobayashi, Ichiro, Alonso, Laura, De Heredia, Cristina Diaz, Kanegane, Hirokazu, Lawitschka, Anita, Seo, Jong Jin, Gonzalez-Vicent, Marta, Diaz, Miguel Angel, Goyal, Rakesh Kumar, Sauer, Martin G., Yesilipek, Akif, Kim, Minsoo, Yilmaz-Demirdag, Yesim, Bhatia, Monica, Khlevner, Julie, Padilla, Erick J. Richmond, Martino, Silvana, Montin, Davide, Neth, Olaf, Molinos-Quintana, Agueda, Valverde-Fernandez, Justo, Broides, Arnon, Pinsk, Vered, Ballauf, Antje, Haerynck, Filomeen, Bordon, Victoria, Dhooge, Catharina, Garcia-Lloret, Maria Laura, Bredius, Robbert G., Kalwak, Krzysztof, Haddad, Elie, Seidel, Markus Gerhard, Duckers, Gregor, Pai, Sung-Yun, Dvorak, Christopher C., Ehl, Stephan, Locatelli, Franco, Goldman, Frederick, Gennery, Andrew Richard, Cowan, Mort J., Roncarolo, Maria-Grazia, Bacchetta, Rosa, Amaya Hernandez, Laura Cristina, Murguia-Favela, Lui, Shearer, William Thoma, Rieux-Laucat, Frédéric, Diaz De Heredia, Cristina, Richmond Padilla, Erick J., and Kałwak, Krzysztof

Subjects
0301 basic medicine, Male, Allergy, medicine.medical_treatment, Medizin, Disease, Hematopoietic stem cell transplantation, SIROLIMUS, Regenerative Medicine, primary immune deficiency, Medicine and Health Sciences, IPEX, Immunology and Allergy, 2.1 Biological and endogenous factors, Enteropathy, Aetiology, POLYENDOCRINOPATHY, Child, Pediatric, CÉLULAS-TRONCO, immunosuppression, Hematopoietic Stem Cell Transplantation, Genetic Diseases, X-Linked, Immunosuppression, Forkhead Transcription Factors, X-LINKED SYNDROME, Allografts, Survival Rate, surgical procedures, operative, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Immune System Diseases, Genetic Diseases, Child, Preschool, hematopoietic stem cell transplantation, Female, hematopoietic stem, neonatal diabetes, FOXP3, Primary Immune Deficiency, Treg cells, enteropathy, genetic autoimmunity, rapamycin, Type 1, Diarrhea, Adult, medicine.medical_specialty, Adolescent, Immunology, Neonatal onset, Article, Disease-Free Survival, 03 medical and health sciences, Neonatal diabete, Clinical Research, Internal medicine, IMMUNODYSREGULATION, medicine, Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation, Diabetes Mellitus, Genetics, Humans, REGULATORY T-CELLS, cell transplantation, Preschool, Retrospective Studies, Immunosuppression Therapy, Transplantation, IMMUNE DYSREGULATION, business.industry, MUTATIONS, Infant, Retrospective cohort study, STEM-CELL TRANSPLANTATION, IPEX syndrome, X-Linked, medicine.disease, Stem Cell Research, BONE-MARROW-TRANSPLANTATION, Treg cell, FOXP3 MUTATIONS, Diabetes Mellitus, Type 1, 030104 developmental biology, ENGRAFTMENT, Mutation, business, Follow-Up Studies
Abstract

Background Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen., GRAPHICAL ABSTRACT

Published
2018

22. A glyphosate micro-emulsion formulation displays teratogenicity in Xenopus laevis

Author

Bonfanti, P, Saibene, M, Bacchetta, R, Mantecca, P, Colombo, A, Bonfanti, P, Saibene, M, Bacchetta, R, Mantecca, P, and Colombo, A

Abstract

Glyphosate is the active ingredient in broad-spectrum herbicide formulations used in agriculture, domestic area and aquatic weed control worldwide. Its market is growing steadily concurrently with the cultivation of glyphosate-tolerant transgenic crops and emergence of weeds less sensitive to glyphosate. Ephemeral and lentic waters near to agricultural lands, representing favorite habitats for amphibian reproduction and early life-stage development, may thus be contaminated by glyphosate based herbicides (GBHs) residues. Previous studies on larval anuran species highlighted increased mortality and growth effects after exposure to different GBHs in comparison to glyphosate itself, mainly because of the surfactants such as polyethoxylated tallow amine present in the formulations. Nevertheless, these conclusions are not completely fulfilled when the early development, characterized by primary organogenesis events, is considered. In this study, we compare the embryotoxicity of Roundup® Power 2.0, a new GBH formulation currently authorized in Italy, with that of technical grade glyphosate using the Frog Embryo Teratogenesis Assay–Xenopus (FETAX). Our results evidenced that glyphosate was not embryolethal and only at the highest concentration (50 mg a.e./L) caused edemas. Conversely, Roundup® Power 2.0 exhibited a 96 h LC50 of 24.78 mg a.e./L and a 96 h EC50 of 7.8 mg a.e./L. A Teratogenic Index of 3.4 was derived, pointing out the high teratogenic potential of the Roundup® Power 2.0. Specific concentration-dependent abnormal phenotypes, such as craniofacial alterations, microphthalmia, narrow eyes and forebrain regionalization defects were evidenced by gross malformation screening and histopathological analysis. These phenotypes are coherent with those evidenced in Xenopus laevis embryos injected with glyphosate, allowing us to hypothesize that the teratogenicity observed for Roundup® Power 2.0 may be related to the improved efficacy in delivering glyphosate to cells, gu

Published
2018

23. Clinical features and follow-up in patients with 22q11.2 deletion syndrome

Author

Cancrini, C, Puliafito, P, Digilio, M, Soresina, A, Martino, S, Rondelli, R, Consolini, R, Ruga, E, Cardinale, F, Finocchi, A, Romiti, Ml, Martire, B, Bacchetta, R, Albano, V, Carotti, A, Specchia, F, Montin, D, Cirillo, E, Cocchi, G, Trizzino, A, Bossi, G, Milanesi, O, Azzari, C, Corsello, G, Pignata, C, Aiuti, A, Pietrogrande, M, Marino, B, Ugazio, A, Plebani, A, Rossi, P, Pierani, P, Gabrielli, A, Danieli, M, De Mattia, D, Sisto, C, Dammacco, F, Ranieri, G, Pession, A, Ricci, G, Minelli, P, Lougaris, V, Badolato, R, Cattaneo, R, Airò, P, Mura, R, Cossu, F, Del Giacco, S, Manconi, P, Consarino, C, Dello Russo, A, Miniero, R, Anastasio, E, Marino, S, Russo, G, Paganelli, R, Sperlì, D, Carpino, L, Aricò, M, Gambineri, E, Lippi, F, Canessa, C, Maggi, E, Romagnani, S, Matucci, A, Vultaggio, A, Gattorno, M, Castagnola, E, Nigro, G, Presta, G, Civino, A, Buzi, F, Gambaretto, G, Fasoli, S, Salpietro, C, Gallizzi, R, Dellepiane, R, Panisi, C, Fabio, G, Carrabba, M, Roncarolo, M, Biondi, A, Vallinoto, C, Poggi, V, Menna, G, Di Nardo, R, Sottile, R, Marone, G, Spadaro, G, Carli, M, Basso, G, Putti, C, Semenzato, G, Agostini, C, D'Angelo, P, Izzi, G, Bertolini, P, Zecca, M, Marseglia, G, Maccario, R, Felici, L, Favre, C, Vecchi, V, Sacchini, P, Rinaldi, G, Livadiotti, S, Simonetti, A, Stabile, A, Duse, M, Iacobini, M, Quinti, I, Fiorilli, M, Moschese, V, Cecere, F, D'Ambrosio, A, De Zan, G, Strafella, S, Tamaro, P, Rabusin, M, Tommasini, A, Tovo, P, De Carli, M, De Carli, S, Nespoli, L, Marinoni, M, Porcellini, A, Lunardi, C, Patuzzo, G, Boner, A, Degani, D, Cancrini, C, Puliafito, P, Digilio, Mc, Soresina, A, Martino, S, Rondelli, R, Consolini, R, Ruga, Em, Cardinale, F, Finocchi, A, Romiti, Ml, Martire, B, Bacchetta, R, Albano, V, Carotti, A, Specchia, F, Montin, D, Cirillo, E, Cocchi, G, Trizzino, A, Bossi, G, Milanesi, O, Azzari, C, Corsello, G, Pignata, C, Aiuti, Alessandro, Pietrogrande, Mc, Marino, B, Ugazio, Ag, Plebani, A, Rossi, P., Cancrini, Caterina, Puliafito, Pamela, Digilio, Maria Cristina, Soresina, Annarosa, Martino, Silvana, Rondelli, Roberto, Consolini, Rita, Ruga, Ezia Maria, Cardinale, Fabio, Finocchi, Andrea, Romiti, Maria Luisa, Martire, Baldassarre, Bacchetta, Rosa, Albano, Veronica, Carotti, Adriano, Specchia, Fernando, Montin, Davide, Cirillo, Emilia, Cocchi, Guido, Trizzino, Antonino, Bossi, Grazia, Milanesi, Ornella, Azzari, Chiara, Corsello, Giovanni, Pignata, Claudio, Pietrogrande, Maria Cristina, Marino, Bruno, Ugazio, Alberto Giovanni, Plebani, Alessandro, Rossi, Paolo, Aiuti, A, Rossi, P, Pierani, P, Gabrielli, A, Danieli, Mg, De Mattia, D, Sisto, C, Dammacco, F, Ranieri, G, Pession, A, Ricci, G, Minelli, P, Lougaris, V, Badolato, R, Cattaneo, R, Airò, P, Mura, Rm, Cossu, F, Del Giacco, S, Manconi, Pe, Consarino, C, Dello Russo, Am, Miniero, R, Anastasio, E, Marino, S, Russo, G, Paganelli, R, Sperlì, D, Carpino, L, Aricò, M, Gambineri, E, Lippi, F, Canessa, C, Maggi, E, Romagnani, S, Matucci, A, Vultaggio, A, Gattorno, M, Castagnola, E, Nigro, G, Presta, G, Civino, A, Buzi, F, Gambaretto, G, Fasoli, S, Salpietro, C, Gallizzi, R, Dellepiane, Rm, Panisi, C, Fabio, G, Carrabba, M, Pietrogrande, M, Roncarolo, Mg, Biondi, A, Vallinoto, C, Poggi, V, Menna, G, Di Nardo, R, Sottile, R, Marone, G, Spadaro, G, Carli, M, Basso, G, Putti, C, Semenzato, G, Agostini, C, D'Angelo, P, Izzi, G, Bertolini, P, Zecca, M, Marseglia, G, Maccario, R, Felici, L, Favre, C, Vecchi, V, Sacchini, P, Rinaldi, G, Livadiotti, S, Simonetti, A, Stabile, A, Duse, M, Iacobini, M, Quinti, I, Fiorilli, M, Moschese, V, Cecere, F, D'Ambrosio, A, De Zan, G, Strafella, S, Tamaro, Paolo, Rabusin, M, Tommasini, A, Tovo, P, De Carli, M, De Carli, S, Nespoli, L, Marinoni, M, Porcellini, A, Lunardi, C, Patuzzo, G, Boner, A, Degani, D., Cancrini, C., Pulisfito, P., Digilio, M. C., Soresina, A., Martino, S., Rondelli, R., Consolini, R., Ruga, E. M., C. a. r. d. i. n. a. l. e., F., Finocchi, A., Romiti, M. L., Martire, B., Bacchetta, R., Albano, V., Carotti, A., Specchia, F., Montin, D., Cocchi, G., Trizzino, A., Bossi, G., Milanesi, O., Azzari, C., Corsello, G., Aiuti, A., Pietrogrande, M. C., Marino, B., Ugazio, A. G., Plebani, A., Digilio, MC, Ruga, EM, Romiti, ML, trizzino, A, Aiuti, Pietrogrande, MC, and Ugazio, AG

Subjects
Male, Pediatrics, 22q11.2 deletion, Delayed Diagnosis, Time Factors, Chromosomes, Human, Pair 22, Developmental Disabilities, digeorge syndrome, Sex Factor, Severity of Illness Index, Retrospective Studie, DiGeorge syndrome, Early Diagnosi, Age Factor, Prospective Studies, Neonatal hypocalcemia, Prospective cohort study, Child, medicine.diagnostic_test, Delayed Diagnosi, Primary immune disorders, Age Factors, del 22q, MIM, Abnormalities, Multiple, Adolescent, Adult, Child, Preschool, DiGeorge Syndrome, Early Diagnosis, Female, Follow-Up Studies, Genetic Testing, Humans, Infant, Infant, Newborn, Monitoring, Physiologic, Retrospective Studies, Risk Assessment, Sex Factors, Young Adult, Disease Progression, Cohort, Abnormalities, Multiple, Pediatrics, Perinatology and Child Health, Human, medicine.medical_specialty, Time Factor, Monitoring, Developmental Disabilitie, Italian Association of Pediatric Haematology and Oncology, Context (language use), Chromosomes, Follow-Up Studie, Severity of illness, medicine, 22q11DS, 22q11.2 deletion syndrome, AIEOP, Mendelian Inheritance in Man, Preschool, Physiologic, Genetic testing, Settore MED/38 - Pediatria Generale e Specialistica, business.industry, Retrospective cohort study, medicine.disease, Newborn, Prospective Studie, Pair 22, business
Abstract

Objective To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. Study design A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. Results The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations ( P = .015) and speech disorders ( P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis. Conclusions Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

Published
2014

25. Toxic effects and ultrastructural damages to Daphnia magna of two differently sized ZnO nanoparticles: Does size matter?

Author

Santo, N, Fascio, U, Torres, F, Guazzoni, N, Tremolada, P, Bettinetti, R, Mantecca, P, Bacchetta, R, Bacchetta, R., MANTECCA, PARIDE, Santo, N, Fascio, U, Torres, F, Guazzoni, N, Tremolada, P, Bettinetti, R, Mantecca, P, Bacchetta, R, Bacchetta, R., and MANTECCA, PARIDE

Abstract

The toxic effects of two differently sized ZnO nanopowders have been studied in Daphnia magna using advanced microscopy techniques. Five nanoZnO suspensions (0.1, 0.33, 1, 3.3 and 10mg/L) were tested. The results of the 48-h acute toxicity tests performed with ZnO<100nm (bZnO) and ZnO<50nm (sZnO) showed slight effects, with EC50 values of 3.1 and 1.9mg/L for bZnO and sZnO, respectively. Specimens exposed to 1 and 3.3mg/L have been microscopically analysed and nanoparticles (NPs) from both concentrations have been found into midgut cells: i) in the microvilli; ii) in endocytic vesicles near the upper cell surface; iii) in some endosomes, as well as in mitochondria, in multivesicular and multilamellar bodies; iv) into the enterocytes' nuclei; v) free in the cytoplasm; vi) in the paracellular space between adjacent cells; vii) into the folded basal plasma membrane, and viii) in the gut muscolaris, suggesting that not only both nanoZnOs are able to interact with the plasmatic membrane of D. magna enterocytes, but also that they are capable to cross epithelial barriers. The ultrastructural changes increased with increasing concentrations and the worst morphological fields came from samples exposed to 3.3mg/L of both nanoZnOs. Morphological effects were qualitatively similar between the two nanomaterials, but they appear to be much more frequent for sZnO NPs. Data from ICP-OES analyses demonstrated that the maximum Zn++ concentration in our tested suspensions was 0.137mg/L, which is well below the reported NOEC for the soluble Zinc. The corresponding Zn-salt exposures (0.1mg/L Zn++) gave 0% of immobilized daphnids for both NPs suggesting that in our test medium nanoZnO toxicity is not driven by their solubilized ions. The large presence of NPs inside midgut cells after only 48-h exposure to nanoZnOs and their effects on the intestinal cells highlighted the toxic potential of these nanomaterials, also suggesting that studies on chronic effects are needed. © 2014 Elsevier L

Published
2014

26. Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization

Author

Fuchs, A., Gliwinski, M., Grageda, N., Spiering, R., Abbas, A.K., Appel, S., Bacchetta, R., Battaglia, M., Berglund, D., Blazar, B., Bluestone, J.A., Bornhauser, M., Brinke, A. Ten, Brusko, T.M., Cools, N., Cuturi, M.C., Geissler, E., Giannoukakis, N., Golab, K., Hafler, D.A., Ham, S.M. van, Hester, J., Hippen, K., Ianni, M. Di, Ilic, N., Isaacs, J., Issa, F., Iwaszkiewicz-Grzes, D., Jaeckel, E., Joosten, I., Klatzmann, D., Koenen, H., Kooten, C. van, Korsgren, O., Kretschmer, K., Levings, M., Marek-Trzonkowska, N.M., Martinez-Llordella, M., Miljkovic, D., Mills, K.H., Miranda, J.P., Piccirillo, C.A., Putnam, A.L., Ritter, T., Roncarolo, M.G., Sakaguchi, S., Sanchez-Ramon, S., Sawitzki, B., Sofronic-Milosavljevic, L., Sykes, M., Tang, Q., Vives-Pi, M., Waldmann, H., Witkowski, P., Wood, K.J., Gregori, S., Hilkens, C.M., Lombardi, G., Lord, P., Martinez-Caceres, E.M., Trzonkowski, P., Fuchs, A., Gliwinski, M., Grageda, N., Spiering, R., Abbas, A.K., Appel, S., Bacchetta, R., Battaglia, M., Berglund, D., Blazar, B., Bluestone, J.A., Bornhauser, M., Brinke, A. Ten, Brusko, T.M., Cools, N., Cuturi, M.C., Geissler, E., Giannoukakis, N., Golab, K., Hafler, D.A., Ham, S.M. van, Hester, J., Hippen, K., Ianni, M. Di, Ilic, N., Isaacs, J., Issa, F., Iwaszkiewicz-Grzes, D., Jaeckel, E., Joosten, I., Klatzmann, D., Koenen, H., Kooten, C. van, Korsgren, O., Kretschmer, K., Levings, M., Marek-Trzonkowska, N.M., Martinez-Llordella, M., Miljkovic, D., Mills, K.H., Miranda, J.P., Piccirillo, C.A., Putnam, A.L., Ritter, T., Roncarolo, M.G., Sakaguchi, S., Sanchez-Ramon, S., Sawitzki, B., Sofronic-Milosavljevic, L., Sykes, M., Tang, Q., Vives-Pi, M., Waldmann, H., Witkowski, P., Wood, K.J., Gregori, S., Hilkens, C.M., Lombardi, G., Lord, P., Martinez-Caceres, E.M., and Trzonkowski, P.

Abstract

Contains fulltext : 191000.pdf (publisher's version ) (Open Access), Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.

Published
2017

29. Effetti di nano ZnO sull’intestino di embrioni di Xenopus laevis

Author

Mantecca, P, Moschini, E, Bonfanti, P, Colombo, A, Camatini, M, Fascio, U, Santo, N, Tremolada, P, Bacchetta, R, MANTECCA, PARIDE, MOSCHINI, ELISA, BONFANTI, PATRIZIA, COLOMBO, ANITA EMILIA, CAMATINI, MARINA CARLA, Bacchetta, R., Mantecca, P, Moschini, E, Bonfanti, P, Colombo, A, Camatini, M, Fascio, U, Santo, N, Tremolada, P, Bacchetta, R, MANTECCA, PARIDE, MOSCHINI, ELISA, BONFANTI, PATRIZIA, COLOMBO, ANITA EMILIA, CAMATINI, MARINA CARLA, and Bacchetta, R.

Published
2012

30. 401 - Hematopoietic Stem/Progenitor Cells and Engineering: T-ALLO10 INFUSION AFTER AβDEPLETED-HSCT IN CHILDREN AND YOUNG ADULTS WITH HEMATOLOGIC MALIGNANCIES: IMPROVED IMMUNE RECONSTITUTION IN THE ABSENCE OF SEVERE GVHD.

Author

Bertaina, A., Bacchetta, R., Shyr, D.C., Saini, G., Lee, J., Kristovich, K., Agarwal, R., Klein, O., Melsop, K., Tate, K., Barbarito, G., Oppizzi, L., Chen, P., Cepika, A., and Roncarolo, M.

Subjects
*YOUNG adults, *PROGENITOR cells, *HEMATOLOGIC malignancies, *ENGINEERING
Published
2023
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31. Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome

Author

Lampasona V, Passerini L, Barzaghi F, Lombardoni C, Bazzigaluppi E, Brigatti C, Bacchetta R, BOSI , EMANUELE, Lampasona, V, Passerini, L, Barzaghi, F, Lombardoni, C, Bazzigaluppi, E, Brigatti, C, Bacchetta, R, and Bosi, Emanuele

Abstract

Autoantibodies to enterocyte antigens harmonin (75 kDa USH1C protein) and villin (actin-binding 95 kDa protein) are associated with the Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome. In this study we evaluated the diagnostic value of harmonin and villin autoantibodies in IPEX and IPEX-like syndromes. Harmonin and villin autoantibodies were measured by a novel Luminescent-Immuno-Precipitation-System (LIPS) quantitative assay, in patients with IPEX, IPEX-like syndrome, Primary Immunodeficiencies (PID) with enteropathy, all diagnosed by sequencing of the FOXP3 gene, and in type 1 diabetes (T1D), celiac disease and healthy blood donors as control groups. Harmonin and villin autoantibodies were detected in 12 (92%) and 6 (46%) of 13 IPEX patients, and in none of the IPEX-like, PID, T1D, celiac patients, respectively. All IPEX patients, including one case with late and atypical clinical presentation, had either harmonin and/or villin autoantibodies and tested positive for enterocyte antibodies by indirect immunofluorescence. When measured in IPEX patients in remission after immunosuppressive therapy or hematopoietic stem cell transplantation, harmonin and villin autoantibodies became undetectable or persisted at low titers in all cases but one in whom harmonin autoantibodies remained constantly high. In one patient, a peak of harmonin antibodies paralleled a relapse phase of enteropathy. Our study demonstrates that harmonin and villin autoantibodies, measured by LIPS, are sensitive and specific markers of IPEX, differentiate IPEX, including atypical cases, from other early childhood disorders associated with enteropathy, and are useful for screening and clinical monitoring of affected children.

Published
2013

34. Effetti di nano ZnO sull’intestino di embrioni di Xenopus laevis

Author

MANTECCA, PARIDE, MOSCHINI, ELISA, BONFANTI, PATRIZIA, COLOMBO, ANITA EMILIA, CAMATINI, MARINA CARLA, Fascio, U, Santo, N, Tremolada, P, Bacchetta, R., Mantecca, P, Moschini, E, Bonfanti, P, Colombo, A, Camatini, M, Fascio, U, Santo, N, Tremolada, P, and Bacchetta, R

Subjects
nano ZnO, Xenopus laevis, sviluppo embrionale, BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
Published
2012

35. Do Surface Modifications Modulate Embryiotoxicity of nano ZnO?

Author

MOSCHINI, ELISA, COLOMBO, ANITA EMILIA, BONFANTI, PATRIZIA, CHIRICO, GIUSEPPE, CAMATINI, MARINA CARLA, MANTECCA, PARIDE, Calabri, L, Rettighieri, L, Bacchetta, R, Santo, N, Fascio, U, Moschini, E, Colombo, A, Bonfanti, P, Calabri, L, Rettighieri, L, Bacchetta, R, Santo, N, Fascio, U, Chirico, G, Camatini, M, and Mantecca, P

Subjects
nano ZnO, embryotoxicity, Xenopus laevis, BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
Published
2012

37. Tossicità di nanoparticelle di Carbonio sullo sviluppo dell’anfibio Xenopus laevis

Author

Fascio, U, Santo, N, Bacchetta, R, Tremolada, P, CHIRICO, GIUSEPPE, CAMATINI, MARINA CARLA, COLOMBO, ANITA EMILIA, MOSCHINI, ELISA, MANTECCA, PARIDE, Fascio, U, Santo, N, Bacchetta, R, Tremolada, P, Chirico, G, Camatini, M, Colombo, A, Moschini, E, and Mantecca, P

Subjects
embriotossicità, nanoparticelle carbonio, Xenopus laevis, BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
Published
2012

38. Teratogenicity of a widely used glyphosate-based herbicide formulation in Xenopus laevis

Author

Saibene, M, Colombo, A, Bonfanti, P, Gornati, R, Bernardini, G, Bacchetta, R, Mantecca, P, SAIBENE, MELISSA, COLOMBO, ANITA EMILIA, BONFANTI, PATRIZIA, BACCHETTA, RENATO, MANTECCA, PARIDE, Saibene, M, Colombo, A, Bonfanti, P, Gornati, R, Bernardini, G, Bacchetta, R, Mantecca, P, SAIBENE, MELISSA, COLOMBO, ANITA EMILIA, BONFANTI, PATRIZIA, BACCHETTA, RENATO, and MANTECCA, PARIDE

Published
2016

40. Mutations in the signal transducer and activator of transcription 3 (STAT3) and diagnostic guidelines for the Hyper-IgE syndrome

Author

Woellner, C., Gertz, M. E., Schaffer, A. A., Lagos, M., Perro, M., Glocker, E. -O, Pietrogrande, M. C., Cossu, F., Franco, J. L., Matamoros, N., Pietrucha, B., Heropolitanska-Pliszka, E., Yeganch, M., Moin, M., Espanol, T., Ehl, S., Gennery, A. R., Abinun, M., Breborowicz, A., Niehues, T., Kilic, S. S., Junker, A., Turvey, S. E., Plebani, A., Sanchez, B., Garty, B-Z, Pignata, C., Cancrini, C., Litzman, J., Sanal, O., Batimann, U., Bacchetta, R., Hsu, A. P., Davis, J. N., Hammarstrom, L., Davies, G. E., Eren, E., Arkwright, P. D., Moilanen, J. S., Viemann, D., Sujoy Khan, Marodi, L., Cant, A. J., Freeman, A. F., Puck, J. M., Holland, S. M., Grimbacher, B., Woellner, C., Gertz, E. M., Schäffer, A. A., Lagos, M., Perro, M., Glocker, E. O., Pietrogrande, M. C., Cossu, F., Franco, J. L., Matamoros, N., Pietrucha, B., Heropolitańska Pliszka, E., Yeganeh, M., Moin, M., Español, T., Ehl, S., Gennery, A. R., Abinun, M., Bręborowicz, A., Niehues, T., Kilic, S. S., Junker, A., Turvey, S. E., Plebani, A., Sánchez, B., Garty, B. Z., Pignata, Claudio, Cancrini, C., Litzman, J., Sanal, O., Baumann, U., Bacchetta, R., Hsu, A. P., Davis, J. N., Hammarström, L., Davies, E. G., Eren, E., Arkwright, P. D., Moilanen, J. S., Viemann, D., Khan, S., Maródi, L., Cant, A. J., Freeman, A. F., Puck, J. M., Holland, S. H., and Grimbacher, B.

Subjects
Hyper-IgE syndrome, STAT3 mutation, TH17 cell, Job syndrome, diagnostic guideline, HIES, Immunodeficiencies
Abstract

BACKGROUND: The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) and severe reductions of T(H)17 cells. OBJECTIVE: To determine whether there is a correlation between the genotype and the phenotype of patients with HIES and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients. METHODS: We collected clinical data, determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong clinical suspicion of HIES and serum IgE >1000 IU/mL. We explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation. RESULTS: In 64 patients, we identified 31 different STAT3 mutations, 18 of which were novel. These included mutations at splice sites and outside the previously implicated DNA-binding and Src homology 2 domains. A combination of 5 clinical features predicted STAT3 mutations with 85% accuracy. T(H)17 cells were profoundly reduced in patients harboring STAT3 mutations, whereas 10 of 13 patients without mutations had low (1000IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: These characteristics plus lack of T(H)17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3.

Published
2010

41. Intensified immunosuppression with ATG reduces graft failure without affecting immune reconstitution or infections in high-risk beta thalassaemia patients after HLA-identical sibling HSCT

Author

Biral E, Cappelli B, Zugna D, Chiesa R, Biffi A, Zito L, Fleischhauer K, Bacchetta R, Fumagalli L, Di Serio C, Roncarolo MG, Aiuti A, Marktel S., CICERI , FABIO, Biral, E, Cappelli, B, Zugna, D, Chiesa, R, Biffi, A, Zito, L, Fleischhauer, K, Bacchetta, R, Fumagalli, L, Di Serio, C, Ciceri, Fabio, Roncarolo, Mg, Aiuti, A, and Marktel, S.

Published
2010

42. Histological changes and micronucleus induction in the zebra mussel Dreissena polymorpha after paraquat exposure

Author

Mantecca, P, Vailati, G, Bacchetta, R, MANTECCA, PARIDE, Bacchetta, R., Mantecca, P, Vailati, G, Bacchetta, R, MANTECCA, PARIDE, and Bacchetta, R.

Abstract

The herbicide paraquat (PQ), still widely used in developing countries, represents a serious risk factor for human and environmental health. To test the sublethal effects of PQ on the freshwater bivalve Dreissena polymorpha, mussels were exposed to 0.125, 0.250, 0.500 mg/L for 7 and 14 days and histologically screened. PQ's genotoxic potential was also determined in haemocytes by the micronucleus, MN, assay. At concentrations > or = 0.250 mg/L, severe lesions, such as cellular vacuolation, lysis and thinness of the germinative epithelia were observed in the digestive gland and testis. A positive trend between the number of granulocytes and all PQ concentrations was observed in both gonads and digestive glands, addressing the inflammatory capacity of this herbicide on these tissues. Mussels exposed to PQ also exhibited a significant MN induction. The spontaneous MN frequencies ranged from 2.75 to 0.425 per cent, while PQ-induced MN rates in treated mussels were between 3.50 and 1.250 per cent. The histopathological effects on the digestive and reproductive systems, as well as the MN induction in the haemocytes, confirmed the cytotoxic and genotoxic effects of PQ also in D. polymorpha.

Published
2006

44. Interleukin-10 Anergized Donor T Cell Infusion Improves Immune Reconstitution without Severe Graft-Versus-Host-Disease After Haploidentical Hematopoietic Stem Cell Transplantation

Author

Bacchetta R, Sartirana C, Lucarelli B, Miqueu P, Stanghellini MTL, Greco R, Velardi A, Aversa F, Martelli MF, Gregori S, Zappone E, Fleischhauer K, Bernardi M, Peccatori J, Roncarolo MG, CICERI , FABIO, Bacchetta, R, Sartirana, C, Lucarelli, B, Miqueu, P, Stanghellini, Mtl, Greco, R, Velardi, A, Aversa, F, Martelli, Mf, Gregori, S, Zappone, E, Fleischhauer, K, Bernardi, M, Peccatori, J, Ciceri, Fabio, and Roncarolo, Mg

Published
2009

45. Termporal, quantitative and functional characteristics of single-KIR positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation

Author

VAGO L, FORNO B, SORMANI M. P, CROCCHIOLO R, ZINO E, DI TERLIZZI S, LUPO STANGHELLINI M. T, MAZZI B, PERNA S. K, BONDANZA A, MIDDLETON D, PALINI A, BERNARDI M, BACCHETTA R, PECCATORI J, ROSSINI S, RONCAROLO M. G, BORDIGNON , CLAUDIO, BONINI C, CICERI, FABIO, AND K. FLEISCHHAUER, Vago, L, Forno, B, SORMANI M., P, Crocchiolo, R, Zino, E, DI TERLIZZI, S, LUPO STANGHELLINI M., T, Mazzi, B, PERNA S., K, Bondanza, A, Middleton, D, Palini, A, Bernardi, M, Bacchetta, R, Peccatori, J, Rossini, S, RONCAROLO M., G, Bordignon, Claudio, Bonini, C, Ciceri, Fabio, and AND K., Fleischhauer

Published
2008

46. Diagnostic criteria for the hyper IgE recurrent infection syndrome/Job’s syndrome/STAT3 deficiency

Author

Woellner C., Gertz E.m., Schaeffer A.A., Lagos M., Perro M., Pietrogrande M.C., Cossu F., Franco J.L., Matamoros N., Pietrucha B., Heropolianska Pliszka E., Yeganeh M., Espanol T., Ehl S., Gennery A.r., Abinun M., Breborowics A., Niehues T., Kilic S.S., Junker A., Turvey S., Plebani A., Sanchez B., Garty B.Z., Cancrini C., Litzman J., Sanal O., Baumann U., Bacchetta R., Hsu A., Hammarstrom L., Davies E.G., Eren E., Arkwright P.D., Moilanen J.S., Viemann D., Khan S., Marodi L., Cant A.M., Puck J.M., Holland S.M., Grimbacher B., PIGNATA, CLAUDIO, Woellner, C., Gertz, E. m., Schaeffer, A. A., Lagos, M., Perro, M., Pietrogrande, M. C., Cossu, F., Franco, J. L., Matamoros, N., Pietrucha, B., Heropolianska Pliszka, E., Yeganeh, M., Espanol, T., Ehl, S., Gennery, A. r., Abinun, M., Breborowics, A., Niehues, T., Kilic, S. S., Junker, A., Turvey, S., Plebani, A., Sanchez, B., Garty, B. Z., Pignata, Claudio, Cancrini, C., Litzman, J., Sanal, O., Baumann, U., Bacchetta, R., Hsu, A., Hammarstrom, L., Davies, E. G., Eren, E., Arkwright, P. D., Moilanen, J. S., Viemann, D., Khan, S., Marodi, L., Cant, A. M., Puck, J. M., Holland, S. M., and Grimbacher, B.

Published
2008

48. Do nanoparticle physico-chemical properties and developmental exposure window influence nano ZnO embryotoxicity in Xenopus laevis?

Author

Bonfanti, P, Moschini, E, Saibene, M, Bacchetta, R, Rettighieri, L, Calabri, L, Colombo, A, Mantecca, P, BONFANTI, PATRIZIA, MOSCHINI, ELISA, SAIBENE, MELISSA, BACCHETTA, RENATO, COLOMBO, ANITA EMILIA, MANTECCA, PARIDE, Bonfanti, P, Moschini, E, Saibene, M, Bacchetta, R, Rettighieri, L, Calabri, L, Colombo, A, Mantecca, P, BONFANTI, PATRIZIA, MOSCHINI, ELISA, SAIBENE, MELISSA, BACCHETTA, RENATO, COLOMBO, ANITA EMILIA, and MANTECCA, PARIDE

Abstract

The growing global production of zinc oxide nanoparticles (ZnONPs) suggests a realistic increase in the environmental exposure to such a nanomaterial, making the knowledge of its biological reactivity and its safe-by-design synthesis mandatory. In this study, the embryotoxicity of ZnONPs (1–100 mg/L) specifically synthesized for industrial purposes with different sizes, shapes (round, rod) and surface coatings (PEG, PVP) was tested using the frog embryo teratogenesis assay-Xenopus (FETAX) to identify potential target tissues and the most sensitive developmental stages. The ZnONPs did not cause embryolethality, but induced a high incidence of malformations, in particular misfolded gut and abdominal edema. Smaller, round NPs were more effective than the bigger, rod ones, and PEGylation determined a reduction in embryotoxicity. Ingestion appeared to be the most relevant exposure route. Only the embryos exposed from the stomodeum opening showed anatomical and histological lesions to the intestine, mainly referable to a swelling of paracellular spaces among enterocytes. In conclusion, ZnONPs differing in shape and surface coating displayed similar toxicity in X. laevis embryos and shared the same target organ. Nevertheless, we cannot exclude that the physico-chemical characteristics may influence the severity of such effects. Further research efforts are mandatory to ensure the synthesis of safer nano-ZnO-containing products.

Published
2015

49. Toxicity evaluation of a new Zn-doped CuO nanocomposite with highly effective antibacterial properties

Author

Mantecca, P, Moschini, E, Bonfanti, P, Fascio, U, Perelshtein, I, Lipovsky, A, Chirico, G, Bacchetta, R, Del Giacco, L, Colombo, A, Gedanken, A, MANTECCA, PARIDE, MOSCHINI, ELISA, BONFANTI, PATRIZIA, CHIRICO, GIUSEPPE, BACCHETTA, RENATO, COLOMBO, ANITA EMILIA, Gedanken, A., Mantecca, P, Moschini, E, Bonfanti, P, Fascio, U, Perelshtein, I, Lipovsky, A, Chirico, G, Bacchetta, R, Del Giacco, L, Colombo, A, Gedanken, A, MANTECCA, PARIDE, MOSCHINI, ELISA, BONFANTI, PATRIZIA, CHIRICO, GIUSEPPE, BACCHETTA, RENATO, COLOMBO, ANITA EMILIA, and Gedanken, A.

Abstract

The increased resistances to conventional antibiotics determine a strong need for new antibacterials, and specific syntheses at the nanoscale promise to be helpful in this field. A novel Zinc-doped Copper oxide nanocomposite (nZn-CuO) has been recently sonochemically synthesized and successfully tested also against multi-drug resistant bacteria. After synthesis and characterization of the physicochemical properties, the new nZn-CuO is here evaluated by the Frog Embyo Teratogenesis Assay-Xenopus test for its toxicological potential and this compared with that of nCuO and nZnO synthesized under the same conditions. No lethal effects are observed, while malformations and growth retardation slightly increase after nZn-CuO exposure. Nevertheless, these effects are smaller than those of nZnO. NP uptake by embryo tissues increase significantly with increasing NP concentrations, while no significant accumulation and adverse effects are seen after exposure to soluble Cu2+ and Zn2+ at the concentrations dissolved from the NPs. Key oxidative response genes are upregulated by nZn-CuO, as well as by nCuO and nZnO, suggesting the common mechanism of action. Considering the enhanced biocidal activity shown by the nanocomposite, together with the results presented in this study, we can affirm that the doping of the metal oxide nanoparticles should be considered a useful tool to engineer a safer nano-antibacterial.

Published
2015

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