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Design of Nanomaterials for Targeted Therapies Guided by Super Resolution Imaging

Periodic Reporting for period 2 - NANOSTORM (Design of Nanomaterials for Targeted Therapies Guided by Super Resolution Imaging)

Reporting period: 2019-08-01 to 2021-01-31

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.
NANOSTORM is a highly multidisciplinary project, combining chemistry, biophysics and biology. Several goals in different disciplines have been achieved here summarized per discipline:
CHEMISTRY: the synthesis of a modular library of new drug carriers have been achieved. This includes both spherical particles and fiber-like objects.
BIOPHYSICS: several super-resolution imaging methods have been devised for the imaging of nanoparticles, their biological targets and nano-bio-interactions.
BIOLOGY: cell-nanoparticles interactions have been studied with microscopy revealing NP localization (were do they go?), stability (how are they?) and drug release (do they perform function?). Moreover the developments of 3D multicellular models (organ-on-a-chip) have been achieved, representing a valid alternative to in vivo experiments.
Two main advancements beyond the state of the art can be envisage. First new microscopy methods to study nanoparticles in vitro and in cells will be made available. Second new insights about NP-cell interactions are and will be obtained (structure-activity relations).
Regarding the methodological part new protocols for imaging and quantifying at the single molecule level the protein corona on NPs, the receptors on the membrane of living cells, the ligands off the surface of nanoparticles have been achieved.
Some preliminary results about structure activity relations are obtained although this is the focus of the remaining part of the project. Correlating the microscopy characterization of NANOSTORM with some functional assay (e.g. organ-on-a-chip) we aim to get a picture of what are the design principles for improved drug carriers and promote the progress of nano medicine in the clinic.
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