The Influence of Maltotriose-Modified Poly(propylene imine) Dendrimers on the Chronic Lymphocytic Leukemia Cells in Vitro: Dense Shell G4 PPI Ida Franiak-Pietryga, † Ewelina Zió lkowska, ‡ Barbara Ziemba, § Dietmar Appelhans, ∥ Brigitte Voit, ∥ Michal Szewczyk, § Joanna Gó ra-Tybor, ‡ Tadeusz Robak, ‡ Barbara Klajnert, § and Maria Bryszewska* ,§ † Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland ‡ Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland § Department of General Biophysics, University of Lodz, Lodz, Poland ∥ Leibniz Institute of Polymer Research Dresden, Dresden, Germany * S Supporting Information ABSTRACT: 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. KEYWORDS: apoptosis, chronic lymphocytic leukemia (CLL), dendrimers, modified dendrimers, poly(propylene imine) (PPI) ■ INTRODUCTION Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe and North America. It usually affects elderly people (81% of patients are over 60), but recently it has been observed more frequently in younger people. Prognosis of survival time and the course of the disease differs among patients, and this can pose a problem in treating this usually benign disease. In about one-third of patients the course of the disease is stable, and early decisions about chemotherapy do not seriously affect survival times. 1,2 However, in most patients, early intensification of symptoms and rapid progression are observed, and survival time is consequently considerably shorter despite prompt treatment. 3,4 For many years, scientists and doctors have been working on introducing the most effective therapy into CLL. Nanotechnology is a new and promising scientific tool in medicine and the pharmaceutical industry where nanoparticles can be used to deliver drugs (hydrophilic and hydrophobic), proteins, vaccines, and different biological macromolecules to the body. This may open a window of therapeutic opportunity for some known drugs. Nanoparticles are better suited for intravenous delivery than larger microparticles. Most narrow capillaries in the body are 5−6 μm in diameter. Therefore, preventing particle-induced embolism, particles distributed in the bloodstream, must be significantly smaller than 5 μm. It can Received: March 11, 2013 Revised: April 26, 2013 Accepted: May 6, 2013 Article pubs.acs.org/molecularpharmaceutics © XXXX American Chemical Society A dx.doi.org/10.1021/mp400142p | Mol. Pharmaceutics XXXX, XXX, XXX−XXX