The Influence of Maltotriose-Modified Poly(propylene imine) Dendrimers on the Chronic Lymphocytic Leukemia Cells in Vitro: Dense Shell G4 PPI

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.

Dendritic Glycopolymer as Drug Delivery System for Proteasome Inhibitor Bortezomib in a Calcium Phosphate Bone Cement: First Steps Toward a Local Therapy of Osteolytic Bone Lesions

“…This great versatility of complex dendritic structures and their derivatives (e.g., dendritic core–shell architectures) allows their impressively successful use in the field of biomedical applications over the last decade . Within this context, dendritic glycopolymers recently outlined their medical, pharmaceutical, and biological potential, for example, as drug delivery system (DDS), polymeric therapeutics and diagnostics, artificial tubulating agent, and anti‐Alzheimer agents . Thus, one can describe the different interaction features of dendritic glycopolymers as chameleon‐like.…”

Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

“…For the successful use of sugar-decorated poly(propylene imine) (PPI) dendrimers as a DDS [10][11][12] and a biological [13][14][15] and stabilizing [16] agent in (bio-)medical applications, one has to not only search for those potential application fields but also understand the cellular uptake and cellular trafficking in various cells. Moreover, a fundamental understanding of their molecular interaction properties against a biological cell membrane and model lipid membranes is mostly unknown.…”

Targeted nanodiamonds for identification of subcellular protein assemblies in mammalian cells

“…When tested on panels of human cells for pharmaceutical applications, densely maltotriose-conjugated dendrimers were the least cytotoxic form of PPI glycodendrimers, compared to unconjugated, partially conjugated and maltose-conjugated PPI dendrimers [53]. Given their low cytotoxicity profile, maltotriose-conjugated dendrimers hold promise as a component of therapeutics for use in humans [54]. The third part of our targeting strategy, the NDs, are also generating increasing interest as therapeutic agents.…”