Hybrid Nanostructured Oligonucleotide Platforms for Biomedical Applications

Project Information

Nano-OligoMed

Grant agreement ID: 778133

DOI

10.3030/778133

Project closed

EC signature date 9 November 2017

Start date 1 December 2017

End date 30 November 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 598 500,00

EU contribution

€ 598 500,00

Coordinated by

UNIVERSITA DEGLI STUDI DI MILANO
Italy

Periodic Reporting for period 2 - Nano-OligoMed (Hybrid Nanostructured Oligonucleotide Platforms for Biomedical Applications)

Reporting period: 2019-12-01 to 2022-11-30

Summary of the context and overall objectives of the project

Nanotechnology (i.e. fabrication and study of properties of objects in the nanometer scale) has received widespread attention in the last several decades due to the technological breakthroughs it has enabled across sectors from electronics to medicine. Providing new nanomaterials with programmed and adaptive properties is one of the ingredients of future personalised medicine.
On the other hand, recent years have seen a tremendous shift of interested towards therapeutic treatments based on RNA/DNA technology (e.g. RNA vaccines, siRNA drugs, gene editing). The present project has the purpose to foster research enabling to join DNA/RNA technologies with the fabrication of functional nanostructures for future, more potent and more selective therapeutic agents which have proven applicability in curing most of the more important human diseases.
Towards the great challenges that nanotechnology arise, the Nano-OligoMed project had the ambition to establish and support a network of international collaboration, enabling a collaborative scientific team to effectively use a diversity of approaches and strategies to design, generate and test innovative nanomaterials for the efficient and safe systemic delivery of oligonucleotide (DNA/RNA or similar)-based therapeutic agents.
To this end, we have set-up a joint multidisciplinary scientific collaborative programme that through exchange, international mobility, and strongly collaborative transfer of knowledge and training activities between 4 European and 3 extra-European countries, brought together leading experts under the field of “nanomaterials in biomedicine”.
Nano-OligoMed allowed the creation of smart nanomaterials that can degrade and thus release a therapeutic cargo only in the presence of a specific molecular or chemical input. This is particularly important because often in cancer cells there is a local change of the chemical environment or an overexpression of a specific biomolecule/receptor. To achieve this objective Nano-OligoMed took advantage of the unique features of nucleic acids as responsive elements to be rationally inserted in the structural framework of the nanomaterial. The presence of DNA and artificial mimicks of nucleic acids as structural elements has allowed to functional materials with unique molecular features.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Different responsive nanocarriers were developed within the project, namely hybrid organic-inorganic nanomaterials (created by incorporating or loading oligonucleotides into the “hard” inorganic structures), lipid nanoparticles or DNA-based nanostructures with responsive properties. Therefore, some of the major scientific results of the project are:
1) the first proof-of-concept construction of hybrid organic-inorganic materials held together by non-covalent programmable interactions based on the well-known base pairing scheme of the genetic code (A-T, G-C) and related variants.
2) The development of responsive lipid-based nanovesicles modified with DNA-based sensing elements that can quantify the presence of clinically relevant nucleic acid biomarkers (miRNAs) widely associated to different cancers.
3) The encapsulation of NAs in different carriers and its release.
4) The creation of hybrid systems responsive to chemical stimuli and recognition events
All the science was possible thanks to a strong collaboration and an efficient exchange of researchers amongst the groups. The young scientist were trained on different aspects of nanotechnology and NA synthesis.In particular the training activities included: i) Training on organic/inorganic nanostructured materials and their application; ii) Training in optical tools, and in materials characterization such as morphology; . III) Training in DNA Nanotechnology from oligonucleotides design, synthesis, to characterization.
Different papers have been published and the results of the project have been widely disseminated within the scientific community through scientific publications and by participating in national and international conferences.
The participation to this international academic networking, the broadening of the research skills, the educational activities, provided to young (PhD students) and senior scientists.
The project had an incredible impact for the creation of new collaborations and fostered the internationalization of the research at the Universities. We are exploiting patents applications to develop further the technologies during the project and writing new applications for funding.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project has seen many objectives realized during the 5 years of research. The main achievements that go well behind the state of art are:
1. For the first time we were able to develop hybrid organosilica systems incorporating oligonucleotide fragments and demonstrated biocompatibility, biodegradability, and responsiveness.
2. The first example of fully supramolecular silica was achieved and incorporation of an aptamer provided a binding site for ATP.
3. Coverage of quatsomes with an inorganic breakable shell realized to create hybrid hard/soft core-shell systems, able to stabilize the organic capsule as well as to decorate the hard silica shell.
4. Stimuli-responsive DNA nanocubes for drug-delivery applications were made and characterized. PNA with appropriate sequences (anti-miR) have been fabricated and used for nanocube and nanosphere production
All these results have been evaluated for exploitation and some market studies are in progress with the SME help. In addition the further development of what we started and scale up of the materials could lead to a new way to carry and release biological molecules and to target specific sites.

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