Engineered Particles for Chemical Communication

Informazioni relative al progetto

EDISON

ID dell’accordo di sovvenzione: 101052997

DOI

10.3030/101052997

Data della firma CE 9 Settembre 2022

Data di avvio 1 Ottobre 2022

Data di completamento 30 Settembre 2027

Finanziato da

• European Research Council (ERC)

Costo totale

€ 2 499 193,00

Contributo UE

€ 2 499 193,00

Coordinato da

UNIVERSITAT POLITECNICA DE VALENCIA
Spain

Periodic Reporting for period 1 - EDISON (Engineered Particles for Chemical Communication)

Periodo di rendicontazione: 2022-10-01 al 2025-03-31

Sintesi del contesto e degli obiettivi generali del progetto

EDISON project aims to the development of communication at the nanoscale and to advance in the understanding of how abiotic micro/nanoparticles can communicate between them and how micro/nanoparticles can communicate with living systems. In this context, an approach for establishing communication at the nanometric level is to mimic how nature communicates. Chemical or molecular communication, based on transmitting and receiving information by means of molecules (chemical messengers) is one of the communication forms used by living organisms. Moreover, many swarm systems found in nature communicate by modifying the environment using a concept called stigmergy. The advantages of nanoparticles communicating with each other are immediately obvious; they constitute the basis of a
dynamically interacting network eventually resulting in certain autonomy of the system. If we would be able to raise the bases for communication between micro/nanoparticles and between micro/nanoparticles and cells, the potential future applications in the biomedical field, environmental research and industry technology are almost unlimited. The project will establish firm handholds for the use of nanoparticles able to communicate from one to another and with cells in different applications. The project will trace, optimize and adapt all the single steps from the idea to its implementation into applicable final systems with the aim of targeting issues that are difficult to address with conventional single particles. The project is divided into three WPs. The first work package (WP1) will create the basic elements for chemical communication. In a more complex situation, WP2 will use the tools of WP1 to develop systems able to establish communication between nanoparticles and living systems. Finally, WP3 will generate nano-systems integrating gated nanoparticles and up-to-date electronics to develop new communication structures.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

1. Studying Chemical Communication Principles
We demonstrated quorum sensing behaviour in an artificial cell population consisting of giant lipid vesicles loaded (GUVs) with sender–receiver machinery (enzymes and responsive biomolecules) (Chem. Commun. 2023, 59, 579-582). In particular, these artificial cell populations are able to (i) exhibit tuneable behaviour depending on their population density and fuel concentration in the medium, and (ii) display spatiotemporal activation patterns depending on their relative distance.
In a second study, we demonstrated the spatiotemporal communication between cell-sized enzyme-based emitters and DNA-based receptors (ACS Cent. Sci. 2024, 10, 1619–1628). In our platform, dynamic DNA nanostructures (compartmentalized into lipid vesicles) change conformation (triplex/duplex) in response to diffusive chemical signals (base/acid) produced by antagonistic senders (after conversion of biomolecular inputs).
In addition, we have published a literature review on communication models (Acc. Chem. Res. 2024, 57, 6, 815–830).
For the development of signal amplification mechanisms, we synergistically combined GUVs as senders and gated mesoporous nanoparticles as receivers (Nano Lett. 2024, 24, 44, 14050–14057) to detect the bacterial toxin α-hemolysin. Altogether, our report presents a new route for engineering sensing systems based on the combination of communicative micro/nanoparticles.
2. Communication Between Nanoparticles and Living Systems
We designed nanomotors based on platinum (Pt)-MS nanoparticles capable of reading molecular signals in the environment (secreted by specific cells) and transform them into autonomous movement (Chem. Mater. 2023, 35, 4412−4426).
Communication between senescent cells and immune cells was achieved using mesoporous silica nanoparticles that generate chemotactic gradients of the immune attractants in the presence of the senescence-associated secretory phenotype (SASP) (Acta Bio. 2024, 176, 405-416). For the first time, a nanodevice capable of recruiting Natural Killer (NK) immune cells to senescent microenvironments via CXCL12-enhanced local concentrations has been validated.
Moreover, we developed a stigmergy strategy that involves nanoparticle-cell-nanoparticle communication (Nano Today 2023, 48, 101692). The targeted therapy was tested in vitro, and in vivo in a triple-negative breast cancer MDA-MB-231 model. The same concept of stigmergy is being applied to eliminate biofilms and bacterial persister cells, using 2 communities of nanoparticles. During this year the synthesis, characterization of prepared nanoparticles has been carried out.
3. Advanced Communication Involving Micro/Nanoparticles and Electronics
Here, we started with the development of specific hardware and software instrumentation for the high-resolution measurement of the electrochemical currents.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

During this first year the project has advanced as expected and the general concept of EDISON is being satisfactorily developed. First achievements which are breakthroughs beyond state-of-art have been achieved.
First, in the field of Studying Chemical Communication Principles, we have developed a model system which (i) exhibits tuneable behaviour depending on their population density and fuel concentration in the medium, and (ii) displays spatiotemporal activation patterns depending on their relative distance (Chem. Commun. 2023, 59, 579-582). This system allows the examination of the collective output based on cell density, fuel concentration and proximity, which are important factors controlling natural quorum sensing behaviour. Also, we have demonstrated the spatiotemporal communication between cell-sized enzyme-based emitters and DNA-based receptors (ACS Cent. Sci. 2024, 10, 1619–1628). Our results provide new possibilities for designing artificial cell consortia with programmable spatio-temporal behaviours based on chemical communication.
In the section of Communication Between Nanoparticles and Living Systems, we have demonstrated that it is possible to develop a nanosystem for the selective delivery of senolytics to senescent cells, which is for the first time based on the specific enzymatic activity of the senescent microenvironment, with potential clinical relevance (Acta Biomaterialia, 2024, 176, 405-416.This study of a senescence-specific context could constitute a means to develop improved senotherapeutic strategies with multiple levels of functionality that might result in potent approaches for precision treatment of senescence-associated diseases.
Also, we developed a ficin@ β-cyclodextrins gated Janus platinum−mesoporous silica nanomotor to effectively disrupt bacterial biofilms via H2O2-induced self-propelled motion, ficin hydrolysis of the extracellular polymeric matrix (EPS) of the biofilm, and controlled pH-triggered cargo (vancomycin) delivery (Chem. Mater. 2023, 35, 4412−4426). The obtained results may provide a long-sought solution to the problem of how to approach the treatment of infections caused by bacterial biofilms. Also, we explored a nanoparticle cooperation strategy that involves nanoparticle-cell-nanoparticle communication in vivo through stigmergy (Nano Today 2023, 48, 101692). The results exhibited the effectiveness of the stigmergy strategy of communication using nanoparticles, confirming that this principle could be applied in vivo enhancing therapy in tumours.

EDISON OVERVIEW