Design of Nanomaterials for Targeted Therapies Guided by Super Resolution Imaging

Project Information

NANOSTORM

Grant agreement ID: 757397

DOI

10.3030/757397

Project closed

EC signature date 25 January 2018

Start date 1 February 2018

End date 31 July 2023

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 497 588,00

EU contribution

€ 1 497 588,00

Coordinated by

TECHNISCHE UNIVERSITEIT EINDHOVEN
Netherlands

Periodic Reporting for period 4 - NANOSTORM (Design of Nanomaterials for Targeted Therapies Guided by Super Resolution Imaging)

Reporting period: 2022-08-01 to 2023-07-31

Summary of the context and overall objectives of the project

Nanomaterials, i.e. materials of a size in the range of a billionth of a meter, are very promising for medical applications such as drug delivery. Nanoparticles can be loaded with drugs and decorated with moieties that will recognize a disease cells resulting in the selective localization of the particle (for example in a tumor) and the consequent specific release of the drug. Therefore the use of nanomaterials for medicine, i.e. nano medicine, is a very popular field of research. However, despite the large investments in nanotechnology-based drug delivery the translation into clinical applications is still unsatisfactory and up to date there are very few nanoamateirals approved for clinical use.
One of the main reasons is the lack of knowledge about the behaviour of nanostructures in the biological environment that makes the rational design of effective drug delivery carriers extremely challenging.
NANOSTORM proposes the solve this issue with an innovative optical imaging technique: super resolution microscopy. Super-resolution microscopy can resolve objects in the nanometer scale such as nanoparticles both in vitro and inside cells and tissues. In NANOSTORM super-resolution microscopy will be used to understand nanoparticles behavior in cells: where do they go? When do they release the drug? Which proteins or molecules do they interact with? This are crucial questions to be able to design the next generation of nano medicines. In particular, in the framework of NANOSTORM novel nanomaterials for the treatment of prostate cancer will be synthesized and evaluated.

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

NANOSTORM is a highly multidisciplinary project, combining chemistry, biophysics and biology. Several goals in have been achieved, both from the scientific and technological point of view.
Within the project a modular library of new drug carriers have been synthesized, including both spherical and fiber-like particles. These have been studied with unprecedented details using super-resolution microscopy, in vitro and in living cells. To achieve that new methods have been devised, innovating microscopy and offering new tailored tools for researcher in the field of nanomedicine. In particular methods to visualize at the molecular level biomarker targets, protein corona, cell targeting and cell trafficking have been developed. This wealth of information on material cell-interactions have been used to advance our fundamental understanding of nanomedicine as well as to design new materials for cell targeting applications.

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)

Two main advancements beyond the state of the art can be envisage. First new microscopy methods to study nanoparticles in vitro and in cells are made available. Second new insights about NP-cell interactions are and will be obtained (structure-activity relations) leading to the rational design of new materials.
The new PAINT super-resolution methods to study cell receptors developed in NANOSTORM exceeded the expectations and allowed to study cell biomarkers interesting for nanomedicine and beyond. In vitro measurements of NANOSTORM open the use of super-resolution microscopy as a material characterisation technique to complement electron and force microscopy.
FInally this knowledge has been used to design novel targeted materials that we tested in functional assay (e.g. organ-on-a-chip) for application in cancer therapy.

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