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04/02/2022

Stable nanovesicles for the delivery of microRNA in cancer treatment

Quatsomes
Grup de recerca en Càncer i Malalties Hematològiques Infantils VHIR

04/02/2022

It is first proof of concept for the delivery of a tumor-suppressive microRNA for the treatment of neuroblastoma, a highly-aggressive pediatric solid tumor of the peripheral nervous system.

A multidisciplinary team with researchers from the Childhood Cancers and Blood Disorders group at Vall d'Hebron Research Institute (VHIR) has designed new nanocapsules (nanovesicles) that allow the encapsulation of a molecule (microRNA) to be administered in the treatment of tumors.

MicroRNAs (also known as miRNAs) are small RNA molecules that can interfere with the stability of other RNA molecules (specifically, messenger RNA). They have many potential therapeutic uses due to the central role they play in major diseases. However, these molecules are still infrequently used in patients due to their instability in the bloodstream and their poor ability to reach specific tissues. In the last few years, the laboratory of Dr. Miguel Segura, researcher at the , has focused on finding the microRNAs with the best therapeutic potential. As Dr. Ariadna Boloix, researcher at the same group at VHIR and first author of the publication says, “it is time to translate our findings for the benefit of patients”. A potential strategy to improve the clinical delivery of miRNAs in the body is to encapsulate them in tiny carriers that compensate its current shortcomings, without side effects and offer other complementary functions.

To this end, researchers have developed a nanostructure, known as quatsomes, composed by two closed lipid layers. In a new publication in Small and highlighted on the “Women in Material Science” Issue of the journal Advanced Materials, an interdisciplinary team of researchers from the Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, the Vall d'Hebron Research Institute (VHIR)-UAB, , the Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Science and Technology (BIST),  the CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), the company Nanomol Technologies SL, the Technion - Israel Institute of Technology and the Institute for Complex Molecular Systems (ICMS), present a newly engineered formulation of quatsomes that have a controlled structure, composition and pH sensitiveness.

“We have collaborated with hospitals, research networks and companies, in this study. The successful results obtained illustrate the importance of collaboration across fields and beyond the academic system”, says Dra. Nora Ventosa, researcher at ICMAB.

These new quatsomes can be coupled with the miRNA and injected intravenously into the body to be delivered in neuroblastoma primary tumors or in frequent sites of metastasis, such as the liver or lung, with a higher success and stability than if the miRNA were injected by itself. Once delivered, the miRNA has an effect on the cell proliferation and survival-related gens in the tumors, decreasing the tumor’s growth rate.

Many properties make quatsomes a good fit for these applications: they are less than 150 nm in size and are stable in a liquid solution for more than 6 months; they also have tunable pH sensitiveness, which means that different pH levels around can trigger different responses.

The production of these nanovesicles has been optimized with their final application in mind and to make sure they can be used in clinics. Through a green and scalable one-step process, named DELOS, researchers have designed a procedure that is fully compliant with Good Manufacturing Practice (GMP) guidelines stablished by the European Union.

In this publication, the functionality of quatsomes in delivering miRNAs, e.g. miR-323a-5p, is demonstrated with a specific extracranial solid tumor common in pediatric cases of cancer known as neuroblastoma, which is responsible for roughly 15 % of all pediatric cancer deaths and lacks therapies for high-risk patients. The results show that quatsomes protect the miRNA from degradation and increase its presence on liver, lung and xenografted neuroblastoma tumors, amongt other tissues. In conclusion, quatsomes is a new potential tool for the administration of RNA-based therapies to clinical practice.

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