Platform Optimisation To Enable NanomaTerIAL safety assessment for rapid commercialisation

Project Information

POTENTIAL

Grant agreement ID: 101092901

DOI

10.3030/101092901

EC signature date 24 November 2022

Start date 1 January 2023

End date 31 December 2026

Funded under

• Digital, Industry and Space

Total cost

€ 2 999 787,50

EU contribution

€ 2 999 787,50

Coordinated by

ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Italy

Periodic Reporting for period 2 - POTENTIAL (Platform Optimisation To Enable NanomaTerIAL safety assessment for rapid commercialisation)

Reporting period: 2024-07-01 to 2025-12-31

Summary of the context and overall objectives of the project

The primary objective of the project is to develop reliable and accessible protocols for the quantification of the possible impact of four different categories of Ad-NMs on environmental and biological matrices. POTENTIAL will generate an integrated platform that provides a series of protocols suitable for monitoring the behavior of a wide range of Ad-NMs, from synthesis to interactions with biological matrices of increasing complexity. The protocols in the validation and development phase will be tested using very different materials and, within the same family, materials with small differences (graphene, quantum dots, biomedical nanocarriers and nano-microplastics). POTENTIAL will engage in silico modeling activities to identify key nano-bio/eco interactions of Ad-NMs in physiological and biological media. This strategy will provide descriptors to develop algorithms for similarity assessment as a basis for enabling the approaches. The platform will finally adopt grouping and read-across approaches that meet regulatory requirements for risk assessment. These methods will be integrated into a methodological framework for the quantitative classification of health and environmental risk.

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

OBJ1-Provide standardised protocols for quantification and characterisation of intrinsic and extrinsic Ad-NMs properties in complex matrices by the development of imaging protocols.
Protocols for the characterization, visualization, and quantification of intrinsic and extrinsic properties of Ad-MMs and NMPs were developed. Some standardized protocols were established for the characterization and quantification of material properties in biological and environmental fluids, including protocols based on advanced microscopy techniques, such as Raman Microspectrometry combined with confocal microscopy and Super-Resolution Imaging Microscopy.
OBJ2-Protocols and methods for isolating and characterizing the biomolecular corona formed on Ad-NMs and NMPs in biological and environmental fluids were established. The objective of developing reliable and exploitable procedures to correlate the biomolecular transformations of Ad-NMs and NMPs with their toxicity has been achieved.
OBJ3 -Develop cost-effective protocols for the quantitative determination of the environmental and health hazard of Ad-NMs reinforcing the 3Rs criteria.
Studies were conducted to characterize and develop an integrated platform for assessing the acute and subacute toxicity of Ad-NMs and MNPs. In particular, we employed 2D and 3D human cellular models to recapitulate the interaction of the materials with intestinal and lung epithelia in vitro, plant cellular models for ecotoxicity studies in vitro, and two animal models that can provide information on organ penetration and function.
OBJ4-Generate grouping and read-across approaches to support risk assessment and SSbD decision making
We have compiled an inventory of established and enhanced Ad-NMs known to affect health and pose ecological risks. There has been a particular focus on how materials' intrinsic characteristics affect their nanobio/eco interactions in complex biological matrices and environmental media. The potential impact of the properties on release, human biodistribution, environmental fate, and human and environmental toxicity has been assessed, and the confidence in this assessment has been evaluated. Moreover, we reviewed existing similarity assessment methods for chemicals and nanomaterials and prioritized methods such as the weighted ordered weighted average and machine-learning approaches, including Histogram-based Gradient Boosting Classification, for further advancement in POTENTIAL. In addition, the relevance of state-of-the-art approaches for grouping nanoforms (e.g. grouping hypotheses, IATA) to addressing the novel properties and interactions of Ad-NMs has been assessed, with a focus on the POTENTIAL case studies.
OBJ5 -Create a crosstalk with project results to international regulatory bodies for standardization and formal validation
We continued to exchange information with the European projects MACRAME, CHIASMA, the EFSA grant NAMS4NANO, and other EU projects. These projects are developing various aspects of animal-free testing for chemicals and nanomaterials. We have exchanged information, protocols, and approaches. As soon as we have significant results, we will engage the SGTA to discuss next steps and how to incorporate them into the regulatory framework.

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)

POTENTIAL's wider impact is to deliver new and efficient methods to develop safer and more sustainable nanotechnology by satisfying the project objectives (OBJ1-5). During the first 36 months, no changes were required to the general impact, the specific expected impacts, or their effects presented in the DoA. The monitoring and impact assessment strategy was also not changed. The methods developed provide a solid basis for generating standardized protocols that facilitate regulatory compliance, thereby shortening time-to-market and increasing productivity, resulting in an economic impact.
Various actions have been undertaken to increase the general population's awareness of Ad-NMs and NMPs, thereby delivering the social impact of POTENTIAL. To this end, the communication and dissemination activities were particularly relevant.