REPOSITORY > RESULTS

Abstract

The tumor microenvironment (TME) is a complex system comprising various non-cancerous cell types and the extracellular matrix. Since tumor cells depend on the TME to sustain their growth and proliferation, targeting the cells and other components of the TME could provide an alternative or combination therapy. Targets in the TME include proteases, whose activity is one of the key elements supporting tumor development and metastasis, and the balance of intra- and extra- cellular concentrations of ions, which is an emerging area for cancer treatment. Here we applied nanotechnology, namely liposomes or aluminum nanoparticles for targeting cysteine proteases – cathepsins S and L – or disruption of the ion balance, respectively.
In the first part of our work, we have prepared a targeting system, based on liposomes, functionalized with an endogenous inhibitor of cysteine cathepsins – stefin A. The prepared system was tested in vitro, where it efficiently bound and inhibited cathepsins S and L. Application of stefin A-functionalized liposomes in vivo in a mouse model of breast cancer revealed its accumulation at the tumor site. Taken together, these results demonstrate a potential for cancer targeting for diagnostic and/or therapeutic approaches.
The second part of this work is focused on aluminum-based nanoparticles and their effect on cancer cells and the tumor microenvironment. Aloohene, an aluminum oxyhydroxide nanoparticle, does not owe its anti-tumor activity to either modulating the extracellular pH or damaging the lysosomes of cancer cells, however, it can cause significant ion imbalance in the cell perimembranous space through the selective adsorption of extracellular anions. Aloohene, θ- and γ-Al2O3 were shown to have a comparable effect on cancer cell lines viability and proliferation, therefore new types of nanoparticles with anti-tumor activity could be prepared using these forms of aluminum oxide.