Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration

Iezzi, Raymond; Guru, Bharath Raja; Glybina, Inna V.; Mishra, Manoj Kumar; Kennedy, Alexander; Kannan, Rangaramanujam M.

doi:10.1016/j.biomaterials.2011.10.010

Cited by 173 publications

(131 citation statements)

References 48 publications

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“…Across the nanoparticle compositions studied, GNPs show the highest potential to increase the radiosensitivity of cells. [3][4][5] A dose enhancement from using GNPs in radiotherapy has already been demonstrated using Monte Carlo simulations; 6 however these simulations are of limited accuracy at micrometer scales, as the continuous physics models used to date break down at small spatial resolutions. 7,8 As one moves towards more accurate microdosimetric measurements of the impact of GNPs, discrete physics models become necessary as they improve the spatial resolution in simulation.…”

Section: Introductionmentioning

confidence: 99%

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

Sakata

Incerti

Bordage

et al. 2016

Journal of Applied Physics

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Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources. Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources. Published by AIP Publishing. [http://dx

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Section: Introductionmentioning

confidence: 99%

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

Sakata

Incerti

Bordage

et al. 2016

Journal of Applied Physics

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“…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]. Significant progress has been made in research on the interactions between dendrimers and living cells or organisms, resulting in commercially available products such as transfection agents (SuperFect from Qiagen and PrioFect from EMD-Merck), markers for rapid heart attack diagnosis (Stratus CS Acute Care from Siemens Healthcare), and anthrax-detecting agents (Alert Ticket from the US Army Research Laboratory) [3].…”

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

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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.

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“…36,37 Como os principais determinantes das propriedades dos dendrímeros, temos a sua geração (relacionada com o peso molecular) e o grupo terminal que afetarão parâmetros como solubilidade, eficácia, bioadesão e farmacocinética. [38][39][40][41][42] A literatura de dendrímeros para a terapia gené-tica ocular ainda é relativamente recente, contando com um número limitado de trabalhos. Dessa maneira, ainda é cedo para predizer o futuro desses sistemas, mesmo já existindo reagentes de transfecção comerciais baseados em dendrímeros (SuperFect ® , Qiagen ® ).…”

Section: Vetores Não Virais Com Base Nanotecnológica Para a Via Ocularunclassified

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

et al. 2016

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Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration

Cited by 173 publications

References 48 publications

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

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

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

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