Development of Chiral Carbon Dots for Boosting Cancer Immunotherapy

Informations projet

ChiralBoost

N° de convention de subvention: 101150852

DOI

10.3030/101150852

Projet clôturé

Date de signature de la CE 14 Mai 2024

Date de début 1 Août 2024

Date de fin 31 Juillet 2026

Financé au titre de

• Marie Skłodowska-Curie Actions (MSCA)

Coût total

Aucune donnée

Contribution de l’UE

€ 208 476,88

Coordonné par

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - ChiralBoost (Development of Chiral Carbon Dots for Boosting Cancer Immunotherapy)

Période du rapport: 2024-08-01 au 2026-07-31

Résumé du contexte et des objectifs généraux du projet

Carbon dots (CDs) are a new class of carbon-based nanomaterials, that are fluorescent. They can be made cheaply and sustainably from biowaste and simple natural molecules, such as amino acids. CDs possess tunable optical properties and low toxicity. For these reasons, they are widely studied for bioimaging, biosensing, drug delivery, and cancer therapy. In immunotherapy, nanoparticles are designed to help the immune system find and attack tumors.
Two problems have slowed progress in this field. First, CDs made in different labs often differ in purity and structure. Even batches from the same lab can differ. Standard methods often cannot detect these differences well. This makes it hard to link how a CD is made to its actual structure, and to how it behaves in the body. As a result, results across the field are often hard to reproduce. Second, many biological molecules and cell surfaces are chiral. They exist in left- and right-handed mirror-image forms. Chirality strongly affects how molecules and nanoparticles interact with living systems, including the immune system. The immune system is very sensitive to molecular shape. But little was known about how giving CDs a defined chirality would affect their interactions with immune cells, and with the biological molecules that first meet a nanoparticle in the body.
The ChiralBoost project tackled both problems. It was carried out at the CNRS Institute of Molecular and Cellular Biology in Strasbourg, through a Marie Skłodowska-Curie Actions Postdoctoral Fellowship. The project first worked to make CD synthesis and purification more rigorous and reproducible. It then used this improved control to produce matched pairs of left- and right-handed chiral CDs. The project tested whether, and how, this chirality affects interactions with immune cells. This was a first step toward understanding whether chirality could become a useful design tool for nanomaterials, to stimulate anti-tumor immune responses more effectively and more safely.
The project had four main objectives: a. To develop reliable, amino-acid-based methods to prepare chiral CDs; b. To study in depth how the structure of these CDs relates to their optical and physicochemical properties. c. To study how chiral CDs interact with immune cells. This includes how proteins in biological fluids coat the nanoparticle surface (“protein corona” formation), and how differently handed CDs are taken up by cells. d. To test whether chiral CDs can help immune cells act against tumor cells.
ChiralBoost tackled the reproducibility problem first. This gives the research community more trustworthy methods and benchmarks for CD synthesis and quality control. This should help the wider carbon nanomaterials field, not just this project. The project then linked CD chirality to real differences in immune-cell behavior. This gives basic knowledge that can help guide the design of safer, more effective nanomaterial tools for cancer immunotherapy, an area of growing importance for public health in Europe and beyond.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The ChiralBoost project had several stages.
First, the team made chiral CDs from amino acids: phenylalanine, tyrosine, and tryptophan. They also used a tartaric acid and tryptophan mixture. Spectroscopy confirmed that the chirality of these starting molecules carried over into the CDs. This gave matched pairs of left- and right-handed CDs. Each was about 5 nanometers across, with blue fluorescence. The team also showed how the choice of starting molecule controls the structure and optical properties of the final CDs. This gives other researchers design rules for making CDs with chosen properties.
Next, the team tested how the CDs interact with immune cells. Human immune cells (macrophages) tolerated the CDs well, even at high doses. Left- and right-handed CDs triggered different levels of immune signaling molecules, called cytokines. This is early evidence that chirality itself can shape how a nanomaterial affects immune cells. The team also studied how proteins in biological fluid coat the CD surface. This process is called protein corona formation. Left- and right-handed CDs were taken up differently by cells. Work to test whether chiral CDs can boost immune cells against tumors is still ongoing. A new PhD student has taken over this part of the work.
The fellowship produced four open-access peer-reviewed papers. They were published in journals including Angewandte Chemie International Edition, Carbon, and Advanced Materials. Results were also presented at two international conferences. These papers give other researchers new, tested methods for making and purifying CDs, and for checking their purity by NMR. This addresses a long-standing problem: many earlier results were hard to compare or reproduce.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Before ChiralBoost, CD research had a basic problem. CDs made by different labs, or in different batches, often differed in purity and structure. Standard methods could not always detect this. This made many published results on CD properties and bioactivity hard to trust or compare.
ChiralBoost tackled this problem directly. The project published a detailed review of CD purification methods, and a new method to check CD purity using NMR. Together, these give the field practical tools to make results more reliable and comparable. A related study linked the structure of the starting molecules directly to the structure and optical properties of the resulting CDs. This gives design rules for making CDs with chosen properties, instead of relying on trial and error.
On the biology side, little was known about whether the chirality of a nanomaterial affects its interaction with immune cells. ChiralBoost provides some of the first evidence that it does. Left- and right-handed CDs triggered different levels of immune signaling molecules in human immune cells, and were taken up differently by cells. This shows that chirality can be a real variable in how a nanomaterial behaves in the body, not just its surface chemistry or size. This opens a new angle for designing nanomaterials for cancer immunotherapy: tuning chirality itself, alongside more commonly studied properties like size and surface charge.