Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe and North America. For many years scientists and doctors have been working on introducing the most effective therapy into CLL as prognosis of survival time and the course of the disease differ among patients, which might pose a problem in treating. Nanotechnology is providing new insights into diagnosis and, compared with conventional treatments, more efficient treatments, which might improve patients' comfort by decreasing side effects. Among the various nanoparticles that are available, dendrimers are one of the most promising. The aim of this study was a preliminary assessment of the clinical value of treating CLL patients with fourth generation poly(propylene imine) (PPI) dendrimers-either unmodified (PPI-G4) or approximately 90% maltotriose-modified (PPI-G4-DS-Mal-III). PPI-G4-DS-Mal-III dendrimers have, in contrast to the cationic PPI-G4, a neutral surface charge and are characterized by low cyto-, geno-, and hematotoxicity in vitro and in vivo. For the in vitro study we used blood mononuclear cells collected from both untreated CLL patients and from healthy donors. Apoptosis was measured by an annexin-V (Ann-V)/propidium iodide (IP) assay, and mitochondrial membrane potential was estimated with use of Mito Tracker Red CMXRos. Presented results confirm the influence of dendrimers PPI-G4 and PPI-G4-DS-Mal-III on apoptosis and CLL lymphocytes viability in in vitro cultures. Both tested dendrimers demonstrated higher cytotoxicity to CLL cells than to healthy donors cells, whereas unmodified dendrimers were more hematotoxic. The surface modification clearly makes glycodendrimers much more suitable for biomedical applications than unmodified PPI-G4; therefore further biological evaluations of these nanoparticles are conducted in our laboratories.

Dendrimers are a relatively new and still not fully examined group of polybranched polymers. In this study polyamidoamine dendrimers with hydroxyl surface groups (PAMAM-OH) of third, fourth and fifth generation (G3, G4 and G5) were examined for their ability to influence the activity of human erythrocyte plasma membrane adenosinetriphosphatases (ATPases). Plasma membrane ATPases are a group of enzymes related, among others, to the maintenance of ionic balance inside the cell. An inhibition of their activity may result in a disturbance of cell functioning. Two of examined dendrimers (G4 and G5) were found to inhibit the activity of Na(+)/K(+) ATPase and Ca(2+) ATPase by 20-30%. The observed effect was diminished when higher concentrations of dendrimers were used. The experiment with the use of pyrene as fluorescent probe sensitive to the changes in microenvironment's polarity revealed that it was an effect of dendrimers' self-aggregation. Additional studies showed that PAMAM-OH dendrimers were able to decrease the fluidity of human erythrocytes plasma membrane. Obtained results suggest that change in plasma membrane fluidity was not caused by the dendrimer-lipid interaction, but dendrimer-protein interaction. Different pattern of influence of dendrimers on ATPases activity and erythrocyte membrane fluidity suggests that observed change in ATPases activity is not a result of dendrimer-lipid interaction, but may be related to direct interaction between dendrimers and ATPases.

There are several barriers to the application of dendriplexes formed by poly(propylene imine) dendrimers and genetic material for gene therapy. One limitation is their interaction with extracellular matrix components such as glucosaminoglycans. These can displace the genetic material from the dendriplexes, affecting their transfection activity. In this study, we analyzed the interaction between dendriplexes and the four main glucosaminoglycans (heparin, heparan sulfate, chondroitin sulfate, and hyaluronic acid) by fluorescence polarization and gel electrophoresis. Dendriplexes were formed by combining three anti-HIV antisense oligodeoxynucleotides with three poly(propylene imine) dendrimers of the fourth generation: unmodified and partially modified with maltose and maltotriose (open shell glycodendrimers). The data showed that the effect of glucosaminoglycans on dendriplexes depends on the glucosaminoglycan type and the oligosaccharide serving as the surface group of the dendrimer. Heparin at physiological concentrations destroys dendriplexes formed by open shell glycodendrimers, but dendriplexes based on unmodified poly(propylene imine) dendrimers are stable in its presence. The other glucosaminoglycans at physiological concentrations cannot destroy dendriplexes formed by any of the dendrimers studied.