WEB Enzyme-Responsive Surface Functionalization of Silica Nanoparticles for Targeted Delivery and Controlled Drug ReleaseTuesday (22.09.2020) 11:50 - 12:05 B: Biomaterials Part of:
Due to the high biocompatibility and simple functionalization of silicon dioxide nanoparticles, they have become one of the best investigated carrier materials in nanomedicine in recent years. Since current therapies for the treatment of cancer constitute a high burden on the organism, the development of new therapies is a central aspect of nanomedicine. Especially the targeted transport and controlled release of the active substances is crucial. Many tumors show an increased expression of the epidermal growth factor receptor (EGFR) and the lysosomal enzyme cathepsin B. Therefore, the active uptake of the nanoparticle controlled by receptor-specific ligands and the release of the active substances in the cell through cathepsin B promise a high selectivity of tumor therapy.
In this work, silicon dioxide nanoparticles were synthesized and surface decorated with two different cathepsin B cleavable peptides and an EGFR targeting ligand to direct nanovectors to the tumor tissue. The receptor induced endocytosis of the nanoparticles was investigated using different cell lines. Moreover, pH dependent measurements demonstrated that the enzyme activity and thus cleaving of biomolecules from nanoparticle surfaces, was enhanced at slightly acidic pH values, as expected for a lysosomal enzyme. Two enzyme- labile amino acid sequences (GVA vs. GFLG) could be characterized and compared regarding their relative cleaving efficiency. GFLG was identified as a promising drug release target and could be used in further studies for the release of therapeutic molecules into tumor tissue.