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

Research output: Contribution to journalArticlepeer-review

4 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 languageEnglish
JournalSmall
DOIs
StatePublished - 16 Nov 2021

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