Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

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

doi:10.1002/smll.202101959

Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

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

^*Corresponding author for this work

Biotechnology and Food Engineering

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English
Journal	Small
DOIs	https://doi.org/10.1002/smll.202101959
State	Published - 16 Nov 2021

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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., Toledo, J. S., Gallego, S., Veciana, J., ... Ventosa, N. (2021). Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics. Small. https://doi.org/10.1002/smll.202101959

@article{26158299caff4899881c9078bdf592ae,

title = "Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics",

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.",

author = "Ariadna Boloix and Natalia Feiner‐Gracia and Mariana K{\"o}ber and Javier Repetto and Rosa Pascarella and Aroa Soriano and Marc Masanas and Nathaly Segovia and Guillem Vargas‐Nadal and Josep Merlo‐Mas and Dganit Danino and Inbal Abutbul‐Ionita and Laia Foradada and Josep Roma and Alba C{\'o}rdoba and Santi Sala and Toledo, {Josep S{\'a}nchez} and Soledad Gallego and Jaume Veciana and Lorenzo Albertazzi and Segura, {Miguel F.} and Nora Ventosa",

year = "2021",

month = nov,

day = "16",

doi = "10.1002/smll.202101959",

language = "英语",

journal = "Small",

issn = "1613-6810",

publisher = "Wiley-VCH Verlag",

}

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, Toledo, JS, Gallego, S, Veciana, J, Albertazzi, L, Segura, MF & Ventosa, N 2021, 'Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics', Small. https://doi.org/10.1002/smll.202101959

TY - JOUR

T1 - Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

AU - Boloix, Ariadna

AU - Feiner‐Gracia, Natalia

AU - Köber, Mariana

AU - Repetto, Javier

AU - Pascarella, Rosa

AU - Soriano, Aroa

AU - Masanas, Marc

AU - Segovia, Nathaly

AU - Vargas‐Nadal, Guillem

AU - Merlo‐Mas, Josep

AU - Danino, Dganit

AU - Abutbul‐Ionita, Inbal

AU - Foradada, Laia

AU - Roma, Josep

AU - Córdoba, Alba

AU - Sala, Santi

AU - Toledo, Josep Sánchez

AU - Gallego, Soledad

AU - Veciana, Jaume

AU - Albertazzi, Lorenzo

AU - Segura, Miguel F.

AU - Ventosa, Nora

PY - 2021/11/16

Y1 - 2021/11/16

N2 - 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.

AB - 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.

U2 - 10.1002/smll.202101959

DO - 10.1002/smll.202101959

M3 - 文章

C2 - 34786859

SN - 1613-6810

JO - Small

JF - Small

ER -

Engineering pH‐Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

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