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.
Highlights
As the world’s population grows almost linearly, by 2050, the fraction of the population above the age of 65 years is expected to be approximately 16% [1]
To understand events occurring in two different murine cell lines, N2a and mHippoE-18, after 24 h of SMT treatment, we examined alterations in cellular responses including activity of mitochondrial dehydrogenases, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, morphological modifications and fractions of apoptotic and dead cells
The standard MTT cytotoxicity assay revealed that the viability of mHippoE-18 and N2a cells, after 24 h incubation with dendrimer SMT1 only slightly decreased, reaching the level of 79% and 76% (N2a) of the control at the highest concentration used (10 μM) (Figures 2 and 3)
Summary
As the world’s population grows almost linearly, by 2050, the fraction of the population above the age of 65 years is expected to be approximately 16% [1]. The incidence of neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and primary brain tumors have a tendency to increase [2]. As it has been pointed out by Mignani et al, around one billion people suffer from disorders related to the central nervous system (CNS) [3]. The most promising feature of NPs is that they are able to efficiently deliver therapeutic agents into difficult to reach regions and to provide the necessary protection to transported drugs This is why nanoparticles are considered as one of the most auspicious and versatile drug delivery systems [7]. Dendrimers can be considered as drugs per se; for example as anti-AD, anti-cancer, anti-prion or anti-inflammatory agents [3]
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