“The beauty of these quatsomes nanovesicles is that they can be easily engineered for the delivery of a variety of nucleic acids. Importantly, they are stable at room temperature, which avoids problems associated to cold chain requirements”, says ICMAB Researcher Nora Ventosa at the Nanomol-Bio Group.

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. 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 offering other complementary functions.

To this end, researchers have developed and designed especially for this application nanostructures, known as quatsomes, composed by two closed lipid layers. In a new publication in Small, which is highlighted in the “Women in Materials Science” Issue of Advanced Materials, researchers present a newly engineered formulation of quatsomes that have a controlled structure, composition and pH sensitiveness. 

The study is the result of an interdisciplinary team of researchers from the Institute of Materials Science of 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 network on Bioengineering, Biomaterails and Nanomedicine (CIBER-BBN), the company Nanomol Technologies SL, the Technion-Israel Institute of Technology and the Institute for Complex Molecular Systems (ICMS).

“In this study we have collaborated with hospitals, research networks and companies. The successful results obtained illustrate the importance of collaboration across fields and beyond the academic system” says Ventosa.

Nanomol-Bio Laboratory / 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.

Sheme of the functionalized quatsome and the interaction with a neuroblastoma cell.

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. “It is time to translate our scientific findings for the benefit of patients” says Ariadna Boloix, VHIR researcher.

In this publication, the functionality of quatsomes in delivering miRNAs 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, amongst other tissues.

ICMAB researchers Mariana Köber and Nora Ventosa / ICMAB

Reference article:

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 de Toledo, Soledad Gallego, Jaume Veciana, Lorenzo Albertazzi, Miguel F. Segura*, Nora Ventosa*
Small, 18, 3, 2022
DOI: 10.1002/smll.202101959

Download the press release in CAT, ESP, ENG.

About the Women in Materials Science Issue in Advanced Materials

To celebrate the upcoming International Women and Girls Day in Science on February 11, and the International Women's Day on March 8, the journals Advanced Materials, Advanced Functional Materials, Advanced Science and Small have prepared a Women in Materials Science Virtual Issue to collect outstanding works created, steered, and led by women scientists around the world, showcasing the high impact these leading researchers have with the research published in these journals. 

Moreover, the featured articles in this issue are made free to read for 3 months starting on 1 February 2022. The article presented here is featured in this issue, which will be frequently updated with the most recent and impactful articles from these top tier journals,

About World Cancer Day

Since 2000, 4 February is the date chosen for the World Cancer Day. It is the global uniting initiative led by the Union for International Cancer Control (UICC). By raising worldwide awareness, improving education and catalysing personal, collective and government action, we are all working together to reimagine a world where millions of preventable cancer deaths are saved and access to life-saving cancer treatment and care is equitable for all - no matter who you are or where you live.

Take a look at some of the ICMAB reseach on cancer

• A Prospective Application in Boron Neutron Capture Therapy (BNCT) for Glioblastoma (25 Jan 2022)
• Development of a radiolabeled nanomaterial to improve current theranostics for cancer (12 Mar 2021)
• Carborane compounds with powerful in vivo anti-glioblastoma activity (19 Feb 2021)
• Bimodal Therapeutic Agents Against Glioblastoma, One of the Most Lethal Forms of Cancer (22 Dec 2020)
• Discover how ICMAB is helping face cancer on #WorldCancerResearchDay (24 Sep 2020)
• Centres of Excellence Against Cancer (7 Sep 2020)
• New 3D printed hydrogels for T-cell growth to be used in cancer immunotherapy (31 Aug 2020)

In the press:

• New cancer radiotherapy and diagnosis mechanisms explained in "The Conversation" (15 Dec 2021)
• Protones para atacar el cáncer y nanomateriales para mejorar el diagnóstico (7 Sep 2021)
• ICMAB cancer research at the new issue of the "CSIC Investiga" magazine (6 Jul 2021)
• Judith, la científica que trata de curar el cáncer con hidrogeles: "Somos pioneros a nivel europeo" (12 May 2021)