Razvoj in in vitro karakterizacija multimodalnih magnetnih nanodelcev za dostavo učinkovin in označevanje celic (Slovene)

In recent decades nanoparticles (NP) based delivery systems emerged. Magnetic nanoparticles (MNPs) due to their multimodal properties can enable targeted drug delivery combined by visualization. Still development of adequate nanoparticles as carrier system  for drug delivery presents a chalenge:  NPs have to be biocompatible, stable in physiological conditions, have to enable sufficient loading capacity and specific release in target cells and should preferentially enable. Finally, the toxicity has to be either minimal (for cell labelling) or specific in case of delivery systems for e.g. cancer therapy. Multimodal MNPs with possibility of high intracellular loading would present an excellent system for different applications, thus we will build on so far acquired knowledge of synthesis, functionalization, characterization in order to further develop appropriate MNPs for labeling and drug delivery applications. Further development of specifically designed MNPs together with protocols for quantification and visualization of NPs interactions with cells and subcellular compartments will open new possibilities in field of nanotoxicology and drug delivery, while better understanding of endocytotic pathways, intracellular fate and permeation of NPs through barriers will assist in development and optimisation of new MNPs for specific applications. Further, long-term nanocytotoxicity studies are crucial for NPs based applications. The project will bring both new protocols for assessing long-term cytotoxicity on realistic biomimetic in vitro models, as well as gain us new insights in analysis of how environmental and biomedically relevant NPs interact and affect the cells. Immediate and long-term toxicity, changes in cell proliferation, generation of reactive oxigen species and immune response will be analyzed in order to obtain clear pictures of relevant mechanisms. Strong collaboration within interdisciplinary partner groups will enable us to gain new scientific knowledge regarding NPs interactions, toxicity and related mechanisms, as well as to transfer the obtained knowledge directly to applications and/or clinical environment.

We have focused on development of magnetic nanoparticles (MNPs) suitable for visualization an drug delivery. Developed multimodal MNPs together with protocols for quantification and visualization of NPs interactions with cells and subcellular compartments open new possibilities in field of cell labeling and drug delivery, while better understanding of endocytotic pathways, intracellular fate and permeation of NPs through barriers will assist in development and application of new MNPs for drug delivery. Further, long-term nanocytotoxicity studies are crucial for NPs based applications. Within the project we developed new protocols for assessing long-term cytotoxicity. In additoin we gained new insights in analysis of how environmental and biomedically relevant NPs interact and affect the chosen cell lines. Cell cycle, proliferation, differentiation, immune response immediate toxicity, ROS generation were analyzed in order to obtain clear pictures of mechanisms behind. Strong collaboration with many partners enabled us to gain new scientific knowledge regarding NPs interactions, toxicity and related mechanisms. Transdisciplinary approach integrated in one project team enabled us integration of new knowledge from diverse scientific fields of physics, material sciences and cell biology. Importantly, the observed highly selective uptake of nanoparticles into cancer urothelial cells opens a posibility for selective targeting

Possible end users of the project results are both biotechnology and pharmaceutical companies as well as medical and research organizations. The results of the project will aid to new protocols for synthesis and functionalisation of advanced nanoparticle, to better understanding of a nanoparticle behavior in the biological systems, and finally to new protocols and better understanding of the long-term effects of NPs on biological systems. One of the major goals was to develop methods for synthesis, functionalization and characterization of nanoparticles as drug delivery systems or for visualization. Magnetic NPs for cell labeling and tracking will aid to faster translation of different methods of tissue regeneration based on transplantation of specific types of cells (e.g. stem cells).