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Nanocarriers and Drug Delivery Group

Biomaterials are useful in drug delivery and targeting, since they can be optimized as controlled release formulations and also as nanoparticles for intracellular drug delivery. Our unique interdisciplinary research program couples both physico-chemical and biological aspects in this area. The research is focused in particular on continuous protein delivery from microencapsulated cells and on nanoparticle-mediated gene delivery and targeted anti-cancer drug research.

Our group performs mechanistic research with nanoparticulate systems with the aim of better understanding the delivery process. Packing of pDNA with polycations is used to form DNA nanoparticles, but structural features of the resulting nanoparticulates are poorly understood. A new time-resolved spectroscopic method was established for DNA packing studies (3,4). The method revealed interesting differences between PLL- and PEI-DNA complexes; the latter shows tightly bound and mobile DNA, whereas PLL-DNA complexes have only tightly bound DNA. The mobile PEI-based complexes have about 100-fold higher activity of transfection per DNA copy delivered to the cell nucleus. We have also demonstrated that the interactions of free PEI with cell surface glycosaminoglycans (GAG) improve DNA transfection, presumably by a decoy effect that reduces the interactions between the complexes and GAGs (5). We also performed a careful mechanistic study to investigate cell penetrating peptides that have been claimed to permeate directly through the cell membrane. In contrast to published reports, we did not observe this. All TAT-peptide variants were endocytosed and trapped within endosomal and lysosomal vesicles (8). 
Our group has also investigated different nanocarriers as new drug delivery systems. For gene delivery, we investigated DNA complexes that were coated with hyaluronic acid (mw 10 kDa). This coating provided gene delivery via CD44-receptor mediated endocytosis (8). Two other receptor mediated drug-targeting systems were investigated: liposomes decorated with EGFR targeted antibodies or neovascularization targeted peptides (1,3). We investigated both systems using various cellular methods, SPECT/CT imaging, mass spectrometric drug distribution analyses, and molecular dynamics simulations. Some targeting efficiency was seen with the antibodies, but the peptide targeting failed. This could be explained using molecular dynamics simulations of the liposomal surface, which suggested that the PEG chains of the liposome shielded the hydrophobic peptide on the liposomal surface. 
Light triggered drug release from liposomes has been achieved by incorporating gold nanoparticles into liposomes (6,7). The gold nanoparticles absorb light, and the energy is transferred as heat to the lipid bilayer that becomes more leaky and releases the drug. High-resolution SAXS measurements reveal that the light induces phase changes in the gold embedded liposomes similar to the changes that are induced by temperature. This suggests that this action is mediated by heat release from the gold nanoparticles. Our data demonstrated drug release from liposomes within the cells, but we did not alter the probe distribution in the cells (i.e., it was retained within endosomal and lysosomal vesicles). 

Selected Publications:


Professor Urtti has led the Centre for Drug Research (CDR) at the University of Helsinki since 2005. Professor Urtti’s has authored more than 220 peer-reviewed articles and 20 patents and patent applications.

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