Bioinorganic intracellular synthesis of photo-responsive bio-camouflaged nanomedicines

Projektinformationen

NanoBioMade

ID Finanzhilfevereinbarung: 865629

DOI

10.3030/865629

EK-Unterschriftsdatum 19 Februar 2020

Startdatum 1 Februar 2021

Enddatum 31 Januar 2027

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 967 000,00

EU-Beitrag

€ 1 967 000,00

Koordiniert durch

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 3 - NanoBioMade (Bioinorganic intracellular synthesis of photo-responsive bio-camouflaged nanomedicines)

Berichtszeitraum: 2024-02-01 bis 2025-07-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Cells can profoundly transform and recycle man-made nanomaterials, to which they had been exposed. To communicate, or in response to exogenous stress, cells generate extracellular vesicles (EVs) which can play crucial roles in multiple physiological processes, including cancer progression. The goal of the NanoBioMade project is to combine both biological processes to deliver cell-made nanomedicines. First, it aims at developping novel strategies to induce bioinorganic intracellular synthesis of nanoparticles (NPs). This should demonstrate that i) NP degradation products can be de novosynthesized NPs and ii) NPs can also be obtained when cells are “fed” with soluble ionic salts. Using living cells as bioreactors may create functional, complex and organism-friendly NPs. NPs with magnetic and photothermal properties will be generated from ion salts precursors.
The second goal is devoted to the biological encapsulation of NPs. For clinical applications, NPs must be efficiently delivered to the target site. The best delivery system is the cell’s innate one, the EVs. Here, groundbreaking physically inspired (hydrodynamic, light) approaches will be proposed and implemented to produce and load EVs with NPs. One specific aim will be to scale-up the production and loading.
The last objective is to exploit biosynthesized NPs and their bio-camouflage within EVs as photothermal agents, used in thermal treatments of cancer. A panel of magnetic nanomaterials, nano-bio-hybrids, vesicles, combination of vesicles and liposomes, will be magnetically or chemotactically delivered to (hetero- and orthotopic) murine tumours, where their action would be triggered by light stimuli to treat cancer.
This project merges works in thermal nano-therapy, EV nano-engineering, and NPs bio-transformations into a new chemical bioinorganic approach with a concrete medical goal and pre-clinical exploration.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The first objective of the NanoBioMade project is to advance the bioinorganic intracellular synthesis of nanoparticles. So far, we have confirmed biosynthesis from nanoparticles degradation with other nanoparticles composition and we have obtained the first proof of concept of magnetic biosynthesis from soluble iron salts only;

The second objective is to develop physically inspired production methods of extracellular vesicles, and try encapsulation of nanoparticles within. So far, we have tested the biological encapsulation of nanoparticles in extracellular vesicles, revealing many methodological difficulties and finally the proof of concept that iron-loaded ferritin bio-particles only can be efficiently trafficked within vesicles, and we have set-up a new method for high-throughput production of vesicles,

The third objective is to exploit biosynthesized nanoparticles and their bio-camouflage within extracellular vesicles in cancer therapy. So far, we have tested the magnetic targeting of highly magnetic nanovectors to (hetero- and orthotopic) murine tumours and we have explored a magneto-mecano-laser multi-modality to study photothermal therapy on cancer spheroids.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Concerning the magnetic biosynthesis (Goal 1), short-term impacts include: - The mechanistic understanding of many aspects of intracellular bioinorganic synthesis; Clues explaining the unknown origin of naturally occurring magnetic nanoparticles (NPs) in humans; - Use of cells as microreactors for synthesis of bioinorganic NPs in scalable processes. Longer-term impacts include: - Novel bioinspired synthesis methodologies in bioinorganic chemistry and materials science; - Potential connection with neurodegenerative diseases; - New generation of bio-assimilable and human-body-friendly products.

Concerning extracellular vesicles (EVs) production and engineering (Goal 2), short-term impacts include: - Development of simple methods for rapid and large-scale EVs production; - Mechanistic aspects of NPs exocytosis and loading into EVs; - Efficient ways to load nanoparticles into EVs. Longer-term impact could resume an universality of the physically-triggered processes, with production and loading to be extended to virtually any type of parent cells, and other cargos (NPs and drugs).

Concerning photothermal therapy of cancer (WP3), short-term impacts include: - the understanding of whether and how EVs derived from stem cells provide enhanced delivery functions to target NPs to tumour cells; - a proof of concept that NPs-mediated therapy can be efficiently provided by EVs. Longer-term impacts would involve the loading of NPs within EVs to serve in therapy in multiple fields of nanomedicine (e.g. immunotherapy, regenerative medicine).

Global reach of NanoBioMade, from biosynthesis to therapy, powered by physically-triggered EVs