Phosphorus-containing dendrimers against α-synuclein fibril formation

Miłowska, Katarzyna; Gabryelak, Teresa; Bryszewska, Maria; Caminade, Anne‐Marie; Majoral, Jean‐Pierre

doi:10.1016/j.ijbiomac.2012.02.003

Cited by 57 publications

(39 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dendrimers could play a role as efficient drug, nucleic acid and contrast agent carriers [3], or they may be used as antipathogenic compounds [4][5][6]. In vitro studies have revealed that these nanoparticles possess the ability to inhibit the fibrillation and aggregation of proteins involved in neurodegenerative disorders [7][8][9]. Importantly, in vivo studies of polyamidoamine (PAMAM) dendrimers have been performed to determine their toxicity to the central nervous system [10], check their ability to localize in inflammatory cells in the brain [11], and show their potential in dendrimer-drug conjugates for the treatment of neuroinflammation [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…1). Since dendrimers are extensively used in anticancer research [30,31] and analyzed for their potential to prevent neurodegenerative disorders [8,9], we used a cancerous neuronal cell line (N2a) for our studies. We investigated several aspects of the cellular response, including cell viability, generation of reactive oxygen species (ROS), alterations in mitochondrial function, morphological modifications, and the induction of apoptosis and necrosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Viologen-phosphorus dendrimers exhibit minor toxicity against a murine neuroblastoma cell line

Łaźniewska

Miłowska

Katir

et al. 2013

Cellular and Molecular Biology Letters

Self Cite

View full text Add to dashboard Cite

Dendrimers containing viologen (derivatives of 4,4'-bipyridyl) units in their structure have been demonstrated to exhibit antiviral activity against human immunodeficiency virus (HIV-1). It has also recently been revealed that novel dendrimers with both viologen units and phosphorus groups in their structure show different antimicrobial, cytotoxic and hemotoxic properties, and have the ability to influence the activity of cholinesterases and to inhibit α-synuclein fibrillation. Since the influence of viologen-phosphorus structures on basic cellular processes had not been investigated, we examined the impact of such macromolecules on the murine neuroblastoma cell line (N2a). We selected three water-soluble viologen-phosphorus (VPD) dendrimers, which differ in their core structure, number of viologen units and number and type of surface groups, and analyzed several aspects of the cellular response. These included cell viability, generation of reactive oxygen species (ROS), alterations in mitochondrial activity, morphological modifications, and the induction of apoptosis and necrosis. The MTT assay results suggest that all of the tested dendrimers are only slightly cytotoxic. Although some changes in ROS formation and mitochondrial function were detected, the three compounds did not induce apoptosis or necrosis. In light of these results, we can assume that the tested VPD are relatively safe for mouse neuroblastoma cells. Although more research on their safety is needed, VPD seem to be promising nanoparticles for further biomedical investigation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viologen-phosphorus dendrimers exhibit minor toxicity against a murine neuroblastoma cell line

Łaźniewska

Miłowska

Katir

et al. 2013

Cellular and Molecular Biology Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…This would indicate that surface amines effect the protein-polymer interaction (note G3.5 PAMAM still has amine groups within its structure, but not at the surface). Two other studies, both using tertiary amine containing dendrimers, showed inhibitory effects of ␣-synuclein aggregation [239,240]. As mentioned before for amyloid ␤ protein, extrapolation of results to fibrillation inhibition mechanisms is difficult.…”

Section: Polymeric Inhibitors Of Protein Aggregationmentioning

confidence: 94%

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

Newland

Werner

et al. 2015

Progress in Polymer Science

View full text Add to dashboard Cite

a b s t r a c tParkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and represents a growing health burden to western societies. Like many neurodegenerative disorders the cause is unknown, however, as the pathogenesis becomes ever more elucidated, it is becoming clear that effective delivery is a key issue for new therapeutics. The versatility of today's polymerization techniques allows the synthesis of a wide range of polymer materials which hold great potential to aid in the delivery of small molecules, proteins, genetic material or cells. In this review, we capture the recent advances in polymer based therapeutics of the central nervous system (CNS). We place the advances in historical context and, furthermore, provide future prospects in line with newly discovered advancements in the understanding of PD and other neurodegenerative disorders. This review provides researchers in the field of polymer chemistry and materials science an up-to-date understanding of the requirements placed upon materials designed for use in the CNS aiding the focus of polymer therapeutic design.

show abstract

“…[31][32][33][34][35][36] Also, PAMAM dendrimers inhibited the fibrillation of α-synuclein, and this effect increased with both generation number and PAMAM concentration. [37][38][39] Among all nanomaterials discussed, dendrimers showed themselves the least toxic. [40][41][42] Dendrimer toxicity in biological system is generally characterized by hemolytic toxicity, cytotoxicity, hematologic toxicity, and interaction with proteins.…”

Section: -22mentioning

confidence: 99%