Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro

Abstract

Dendrimers as drug carriers can be utilized for drugs and siRNA delivery in central nervous system (CNS) disorders, including various types of cancers, such as neuroblastomas and gliomas. They have also been considered as drugs per se, for example as anti-Alzheimer’s disease (AD), anti-cancer, anti-prion or anti-inflammatory agents. Since the influence of carbosilane–viologen–phosphorus dendrimers (SMT1 and SMT2) on the basic cellular processes of nerve cells had not been investigated, we examined the impact of two generations of these hybrid macromolecules on two murine cell lines—cancer cell line N2a (mouse neuroblastoma) and normal immortalized cell line mHippoE-18 (embryonic mouse hippocampal cell line). We examined alterations in cellular responses including the activity of mitochondrial dehydrogenases, the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, and morphological modifications and fractions of apoptotic and dead cells. Our results show that both dendrimers at low concentrations affected the cancer cell line more than the normal one. Also, generation-dependent effects were found: the highest generation induced greater cytotoxic effects and morphological modifications. The most promising is that the changes in mitochondrial membrane potential and transmission electron microscopy (TEM) images indicate that dendrimer SMT1 can reach mitochondria. Thus, SMT1 and SMT2 seem to have potential as nanocarriers to mitochondria or anti-cancer drugs per se in CNS disorders.

Combination of Copper Metallodendrimers with Conventional Antitumor Drugs to Combat Cancer in In Vitro Models

“…It is well known that cytotoxicity effects can be tightly connected with intracellular reactive oxygen species generation [ 38 ]. Considering the important role of ROS production for cell viability and the possibility of using this parameter as an indicator of apoptosis regulation [ 39 ], we studied the changes of intracellular ROS level with the presence of dendrimer/drug complexes.…”

A Glimpse into Dendrimers Integration in Cancer Imaging and Theranostics

“…Aleksandra Szwed et al studied the interaction mechanisms of hybrid carbosilane–viologen–phosphorus dendrimers (SMT1 and SMT2) with two different murine cell lines. These dendrimers present two distinct cationic groups (internal and outer) that are specific for mitochondria, inducing perturbations in mitochondrial membrane potential and the formation of reactive oxigen species (ROS) [ 109 ].…”

Hybrid phosphorus–viologen dendrimers as new soft nanoparticles: design and properties

“…Szwed et al 76 examined the carbosilane-viologen-phosphorus dendrimers (SMT1 and SMT2, see Figure 4) effects on the basic cellular processes of nerve cells: cancer cell line N2a (mouse neuroblastoma) and normal immortalized cell line mHippoE-18 (embryonic mouse hippocampal cell line). Interestingly, these dendrimers are more toxic on these cancer cell lines than on normal cell lines at low concentrations.…”

“…To summarize these two hybrid carbosilane-viologenphosphorus dendrimers, SMT1 and SMT2 can be considered as possible nanocarriers to mitochondria and offer the possibility to be used as anti-cancer drugs per se in CNS disorders. 76…”