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2. Order from disorder with intrinsically disordered peptide amphiphiles

Author

Jacoby, Guy, Asher, Merav Segal, Ehm, Tamara, Ionita, Inbal Abutbul, Shinar, Hila, Azoulay-Ginsburg, Salome, Danino, Dganit, Kozlov, Michael M., Amir, Roey J., and Beck, Roy

Subjects
Condensed Matter - Soft Condensed Matter, Condensed Matter - Mesoscale and Nanoscale Physics, Physics - Biological Physics, Physics - Chemical Physics
Abstract

Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block-copolymers. Herein, we present new peptide amphiphiles comprised of an intrinsically disordered peptide conjugated to two variants of hydrophobic dendritic domains. These molecules termed intrinsically disordered peptide amphiphiles (IDPA), exhibit a sharp pH-induced micellar phase-transition from low-dispersity spheres to extremely elongated worm-like micelles. We present an experimental characterization of the transition and propose a theoretical model to describe the pH-response. We also present the potential of the shape transition to serve as a mechanism for the design of a cargo hold-and-release application. Such amphiphilic systems demonstrate the power of tailoring the interactions between disordered peptides for various stimuli-responsive biomedical applications., Comment: 27 pages, 4 figures, supplementary information file

Published
2021
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4. Ferritin is secreted via 2 distinct nonclassical vesicular pathways

Author

Truman-Rosentsvit, Marianna, Berenbaum, Dina, Spektor, Lior, Cohen, Lyora A., Belizowsky-Moshe, Shirly, Lifshitz, Lena, Ma, Jing, Li, Wei, Kesselman, Ellina, Abutbul-Ionita, Inbal, Danino, Dganit, Gutierrez, Lucia, Li, Huihui, Li, Kuanyu, Lou, Huifang, Regoni, Maria, Poli, Maura, Glaser, Fabian, Rouault, Tracey A., and Meyron-Holtz, Esther G.

Published
2018
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5. On the startup behavior of wormlike micellar networks: The effect of different salts bound to the same surfactant molecule

Author

Rossana Pasquino, Pietro Renato Avallone, Salvatore Costanzo, Ionita Inbal, Dganit Danino, Vincenzo Ianniello, Giovanni Ianniruberto, Giuseppe Marrucci, Nino Grizzuti, Pasquino, R., Renato Avallone, P., Costanzo, S., Inbal, I., Danino, D., Ianniello, V., Ianniruberto, G., Marrucci, G., and Grizzuti, N.

Subjects
Mechanics of Materials, Mechanical Engineering, General Materials Science, Condensed Matter Physics
Abstract

We report on shear startup data for two wormlike micellar solutions, differing only in concentration and type of two binding aromatic sodium salts. The surfactant molecule is cetylpiridinium chloride at a fixed concentration (100 mM). Sodium salicylate (NaSal) and diclofenac sodium (Diclo) are used as binding salts at concentrations 68 mM NaSal and 52 mM Diclo such that both systems are fully entangled and their linear viscoelastic response is essentially identical. Both systems show the linear response typical of a wormlike micellar solution, with terminal behavior at low frequencies, a well-defined moduli crossover, and a plateau modulus. In the nonlinear regime, however, the behavior of the two systems is totally different, suggesting that the molecular structure difference of the salts and their binding activity to the surfactant molecule are both crucial to determine the fast flow behavior. The NaSal solution shows a very complex rheological response, with strain hardening and very sharp stress peaks, whereas the solution containing Diclo behaves much like ordinary linear polymers, exhibiting pronounced overshoots as well as moderate undershoots in the transient shear viscosity, before approaching the steady state. This polymerlike behavior has also been proved by successfully comparing data with predictions of a constitutive equation recently adopted for both entangled polymers and linear wormlike micelles. As far as NaSal is concerned, a phenomenological model based on rubber network theory is developed, which describes the flow singularities. A physical interpretation of the different behavior in the nonlinear regime is also suggested.

Published
2023
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7. Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

Author

Boloix, Ariadna, Feiner-Gracia, Natalia, Köber, Mariana, Repetto, Javier, Pascarella, Rosa, Soriano, Aroa, Masanas, Marc, Segovia, Nathaly, Vargas-Nadal, Guillem, Merlo-Mas, Josep, Danino, Dganit, Abutbul-Ionita, Inbal, Foradada, Laia, Roma, Josep, Córdoba, Alba, Sala, Santi, de Toledo, Josep Sánchez, Gallego, Soledad, Veciana, Jaume, Albertazzi, Lorenzo, Segura, Miguel F., Ventosa, Nora, Boloix, Ariadna, Feiner-Gracia, Natalia, Köber, Mariana, Repetto, Javier, Pascarella, Rosa, Soriano, Aroa, Masanas, Marc, Segovia, Nathaly, Vargas-Nadal, Guillem, Merlo-Mas, Josep, Danino, Dganit, Abutbul-Ionita, Inbal, Foradada, Laia, Roma, Josep, Córdoba, Alba, Sala, Santi, de Toledo, Josep Sánchez, Gallego, Soledad, Veciana, Jaume, Albertazzi, Lorenzo, Segura, Miguel F., and Ventosa, Nora

Abstract

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics.

Published
2022

8. Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

Author

Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (España), Matem lo Bitxo, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Boloix, Ariadna [0000-0002-1648-5589], Köber, Mariana [0000-0001-9962-7900], Soriano, Aroa [0000-0001-9659-1471], Masanas, Marc [0000-0002-2249-8554], Segovia, Nathaly [0000-0001-8814-6095], Vargas Nadal, Guillem [0000-0003-4383-1325], Merlo Mas, Josep [0000-0002-3698-6655], Danino, Dganit [0000-0002-9782-4940], Foradada, Laia [0000-0002-0589-4360], Roma, Josep [0000-0001-7692-6123], Toledo, Josep Sánchez de [0000-0002-1034-1920], Gallego, Soledad [0000-0002-4712-9624], Veciana, Jaume [0000-0003-1023-9923], Albertazzi, Lorenzo [0000-0002-6837-0812], Segura, Miguel F. [0000-0003-0916-3618], Ventosa, Nora [0000-0002-8008-4974], Boloix, Ariadna, Feiner-Gracia, Natalia, Köber, Mariana, Repetto, Javier, Pascarella, Rosa, Soriano, Aroa, Masanas, Marc, Segovia, Nathaly, Vargas Nadal, Guillem, Merlo Mas, Josep, Danino, Dganit, Abutbul-Ionita, Inbal, Foradada, Laia, Roma, Josep, Córdoba, Alba, Sala Vergés, Santiago, Toledo, Josep Sánchez de, Gallego, Soledad, Veciana, Jaume, Albertazzi, Lorenzo, Segura, Miguel F., Ventosa, Nora, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (España), Matem lo Bitxo, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Boloix, Ariadna [0000-0002-1648-5589], Köber, Mariana [0000-0001-9962-7900], Soriano, Aroa [0000-0001-9659-1471], Masanas, Marc [0000-0002-2249-8554], Segovia, Nathaly [0000-0001-8814-6095], Vargas Nadal, Guillem [0000-0003-4383-1325], Merlo Mas, Josep [0000-0002-3698-6655], Danino, Dganit [0000-0002-9782-4940], Foradada, Laia [0000-0002-0589-4360], Roma, Josep [0000-0001-7692-6123], Toledo, Josep Sánchez de [0000-0002-1034-1920], Gallego, Soledad [0000-0002-4712-9624], Veciana, Jaume [0000-0003-1023-9923], Albertazzi, Lorenzo [0000-0002-6837-0812], Segura, Miguel F. [0000-0003-0916-3618], Ventosa, Nora [0000-0002-8008-4974], Boloix, Ariadna, Feiner-Gracia, Natalia, Köber, Mariana, Repetto, Javier, Pascarella, Rosa, Soriano, Aroa, Masanas, Marc, Segovia, Nathaly, Vargas Nadal, Guillem, Merlo Mas, Josep, Danino, Dganit, Abutbul-Ionita, Inbal, Foradada, Laia, Roma, Josep, Córdoba, Alba, Sala Vergés, Santiago, Toledo, Josep Sánchez de, Gallego, Soledad, Veciana, Jaume, Albertazzi, Lorenzo, Segura, Miguel F., and Ventosa, Nora

Abstract

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics.

Published
2022

10. Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

Author

Boloix, Ariadna, primary, Feiner‐Gracia, Natalia, additional, Köber, Mariana, additional, Repetto, Javier, additional, Pascarella, Rosa, additional, Soriano, Aroa, additional, Masanas, Marc, additional, Segovia, Nathaly, additional, Vargas‐Nadal, Guillem, additional, Merlo‐Mas, Josep, additional, Danino, Dganit, additional, Abutbul‐Ionita, Inbal, additional, Foradada, Laia, additional, Roma, Josep, additional, Córdoba, Alba, additional, Sala, Santi, additional, Toledo, Josep Sánchez, additional, Gallego, Soledad, additional, Veciana, Jaume, additional, Albertazzi, Lorenzo, additional, Segura, Miguel F., additional, and Ventosa, Nora, additional

Published
2021
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11. Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Author

Jacoby, Guy, primary, Segal Asher, Merav, additional, Ehm, Tamara, additional, Abutbul Ionita, Inbal, additional, Shinar, Hila, additional, Azoulay-Ginsburg, Salome, additional, Zemach, Ido, additional, Koren, Gil, additional, Danino, Dganit, additional, Kozlov, Michael M., additional, Amir, Roey J., additional, and Beck, Roy, additional

Published
2021
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12. Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Author

Elia, Uri, primary, Rotem, Shahar, additional, Bar-Haim, Erez, additional, Ramishetti, Srinivas, additional, Naidu, Gonna Somu, additional, Gur, David, additional, Aftalion, Moshe, additional, Israeli, Ma’ayan, additional, Bercovich-Kinori, Adi, additional, Alcalay, Ron, additional, Makdasi, Efi, additional, Chitlaru, Theodor, additional, Rosenfeld, Ronit, additional, Israely, Tomer, additional, Melamed, Sharon, additional, Abutbul Ionita, Inbal, additional, Danino, Dganit, additional, Peer, Dan, additional, and Cohen, Ofer, additional

Published
2021
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13. A lipid nanoparticle RBD-hFc mRNA vaccine protects hACE2 transgenic mice against lethal SARS-CoV-2 infection

Author

Elia, Uri, primary, Rotem, Shahar, additional, Bar-Haim, Erez, additional, Ramishetti, Srinivas, additional, Naidu, Gonna Somu, additional, Gur, David, additional, Aftalion, Moshe, additional, Israeli, Ma’ayan, additional, Bercovich-Kinori, Adi, additional, Alcalay, Ron, additional, Makdasi, Efi, additional, Chitlaru, Theodor, additional, Rosenfeld, Ronit, additional, Israely, Tomer, additional, Melamed, Sharon, additional, Ionita, Inbal Abutbul, additional, Danino, Dganit, additional, Peer, Dan, additional, and Cohen, Ofer, additional

Published
2021
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14. Impact of Chemical Composition on the Nanostructure and Biological Activity of α-Galactosidase-Loaded Nanovesicles for Fabry Disease Treatment

Author

Tomsen-Melero, Judit, primary, Passemard, Solène, additional, García-Aranda, Natalia, additional, Díaz-Riascos, Zamira Vanessa, additional, González-Rioja, Ramon, additional, Nedergaard Pedersen, Jannik, additional, Lyngsø, Jeppe, additional, Merlo-Mas, Josep, additional, Cristóbal-Lecina, Edgar, additional, Corchero, José Luis, additional, Pulido, Daniel, additional, Cámara-Sánchez, Patricia, additional, Portnaya, Irina, additional, Ionita, Inbal, additional, Schwartz, Simó, additional, Veciana, Jaume, additional, Sala, Santi, additional, Royo, Miriam, additional, Córdoba, Alba, additional, Danino, Dganit, additional, Pedersen, Jan Skov, additional, González-Mira, Elisabet, additional, Abasolo, Ibane, additional, and Ventosa, Nora, additional

Published
2021
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16. Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Dong, Yizhou, Dorkin, Joseph Robert, Wang, Weiheng, Chang, Philip, Webber, Matthew, Tang, Benjamin C., Yang, Jung H, Langer, Robert S, Anderson, Daniel Griffith, Abutbul-Ionita, Inbal, Danino, Dganit, DeRosa, Frank, Heartlein, Michael, Chang, Philip H., Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Dong, Yizhou, Dorkin, Joseph Robert, Wang, Weiheng, Chang, Philip, Webber, Matthew, Tang, Benjamin C., Yang, Jung H, Langer, Robert S, Anderson, Daniel Griffith, Abutbul-Ionita, Inbal, Danino, Dganit, DeRosa, Frank, Heartlein, Michael, and Chang, Philip H.

Abstract

Safe and effective delivery is required for siRNA and mRNA-based therapeutics to reach their potential. Here, we report on the development of poly(glycoamidoamine) brush nanoparticles as delivery vehicles for siRNA and mRNA. These polymers were capable of significant delivery of siRNA against FVII and mRNA-encoding erythropoietin (EPO) in mice. Importantly, these nanoparticles were well-tolerated at their effective dose based on analysis of tissue histology, systemic cytokine levels, and liver enzyme chemistry. The polymer brush nanoparticles reported here are promising for therapeutic applications., MIT-Harvard Center of Cancer Nanotechnology Excellence (Grant U54-CA151884), National Heart, Lung, and Blood Institute (Contract HHSN268201000045C), Shire Pharmaceuticals, Alnylam Pharmaceuticals (Firm), National Institutes of Health (U.S.) (Grants R01-EB000244-27, 5- R01-CA132091-04, and R01-DE016516-03), National Institute for Biomedical Imaging and Bioengineering (U.S.) (Postdoctoral Fellowship 1F32EB017625)

Published
2017

18. Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo

Author

Dong, Yizhou, primary, Dorkin, J. Robert, additional, Wang, Weiheng, additional, Chang, Philip H., additional, Webber, Matthew J., additional, Tang, Benjamin C., additional, Yang, Junghoon, additional, Abutbul-Ionita, Inbal, additional, Danino, Dganit, additional, DeRosa, Frank, additional, Heartlein, Michael, additional, Langer, Robert, additional, and Anderson, Daniel G., additional

Published
2016
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20. Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease.

Author

Tomsen-Melero, Judit, Moltó-Abad, Marc, Merlo-Mas, Josep, Díaz-Riascos, Zamira V., Cristóbal-Lecina, Edgar, Soldevila, Andreu, Altendorfer-Kroath, Thomas, Danino, Dganit, Ionita, Inbal, Pedersen, Jan Skov, Snelling, Lyndsey, Clay, Hazel, Carreño, Aida, Corchero, José L., Pulido, Daniel, Casas, Josefina, Veciana, Jaume, Schwartz Jr., Simó, Sala, Santi, and Font, Albert

Subjects
*ANGIOKERATOMA corporis diffusum, *ENZYME replacement therapy, *GALACTOSIDASES, *LYSOSOMAL storage diseases, *CENTRAL nervous system, *SYMPTOMS
Abstract

The central nervous system represents a major target tissue for therapeutic approach of numerous lysosomal storage disorders. Fabry disease arises from the lack or dysfunction of the lysosomal alpha-galactosidase A (GLA) enzyme, resulting in substrate accumulation and multisystemic clinical manifestations. Current enzyme replacement therapies (ERTs) face limited effectiveness due to poor enzyme biodistribution in target tissues and inability to reach the brain. We present an innovative drug delivery strategy centered on a peptide-targeted nanoliposomal formulation, designated as nanoGLA, engineered to selectively deliver a recombinant human GLA (rhGLA) to target tissues. In a Fabry mouse model, nanoGLA demonstrated improved efficacy, inducing a notable reduction in Gb3 deposits in contrast to non-nanoformulated GLA, even in the brain, highlighting the potential of the nano-GLA to address both systemic and cerebrovascular manifestations of Fabry disease. The EMA has granted the Orphan Drug Designation to this product, underscoring the potential clinical superiority of nanoGLA over authorized ERTs and encouraging to advance it toward clinical translation. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics.

Author

Boloix A, Feiner-Gracia N, Köber M, Repetto J, Pascarella R, Soriano A, Masanas M, Segovia N, Vargas-Nadal G, Merlo-Mas J, Danino D, Abutbul-Ionita I, Foradada L, Roma J, Córdoba A, Sala S, de Toledo JS, Gallego S, Veciana J, Albertazzi L, Segura MF, and Ventosa N

Subjects
Humans, Hydrogen-Ion Concentration, MicroRNAs chemistry, Nanoparticles chemistry, Neoplasms drug therapy, Neoplasms therapy
Abstract

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

Published
2022
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