Efficient, Non-Toxic Hybrid PPV-PAMAM Dendrimer as a Gene Carrier for Neuronal Cells

Rodrigo, Ana C.; Rivilla, Iván; Pérez-Martínez, Francisco C.; Monteagudo, S.; Ocana, Vanessa; Guerra, Javier Miguel Martín; Garcı́a-Martı́nez, Joaquín C.; Merino, Sonia; Sánchez-Verdú, Prado; Ceña, Valentı́n; Rodríguez‐López, Julián

doi:10.1021/bm1014987

Cited by 52 publications

(44 citation statements)

References 58 publications

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“…To evaluate whether cofilin plays a central role during excitotoxic neuronal death, we acutely knocked down cofilin from rat cortical neurons by using a specific siRNA delivered to the neurons using a recently described dendrimer (TGD) (Rodrigo et al. 2011).…”

Section: Resultsmentioning

confidence: 99%

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Cofilin activation mediates Bax translocation to mitochondria during excitotoxic neuronal death

Posadas

Pérez-Martínez²,

Guerra

et al. 2012

Journal of Neurochemistry

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J. Neurochem. (2012) 120, 515–527. Abstract During excitotoxic neuronal death, Bax translocates to the mitochondria where it plays an important role by contributing to the release of proapoptotic factors. However, how Bax translocates to the mitochondria during excitotoxicity remains poorly understood. Herein, our data suggest the presence of a novel signalling mechanism by which NMDA receptor stimulation promotes Bax translocation. This signalling pathway is triggered by dephosphorylation of cofilin. Once dephosphorylated, cofilin might interact physically with Bax acting as a carrier for it, translocating it to the mitochondria, where it contributes to mitochondrial membrane despolarization, permeabilization and to the release of apoptotic factors, thus leading to neuronal death. Lack‐of‐function studies indicate that only the Slingshot family of phosphatases, more specifically the enzyme Slingshot 1L phosphatase, but not cronophin participates in the cofilin activation process during excitotoxicity. Indeed, cofilin‐mediated Bax translocation seems to be a key event in excitotoxic neuronal death as knock down of either cofilin or Slingshot 1L phosphatase has a marked neuroprotective effect on NMDA‐mediated neuronal death. This novel biochemical pathway may therefore be a good target to develop future therapeutic molecules for neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

“…In this study, we knocked down cofilin from primary rat cortical neurons using small‐interfering RNA (siRNA), which was delivered to the neurons using a non‐viral vector (a dendrimer) with a known high transfection efficiency in neurons (Rodrigo et al. 2011), and studied the effect of this knock down on excitotoxic neuronal death.…”

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confidence: 99%

Cofilin activation mediates Bax translocation to mitochondria during excitotoxic neuronal death

Posadas

Pérez-Martínez²,

Guerra

et al. 2012

Journal of Neurochemistry

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“…Effective control of molecular assembly has promisinga pplications in differentt echnological and scientific fields. For instance, someb iomedical applications, such as biosensing, bioimaging, [14][15][16][17][18][19] and gene and drug delivery, [2,20,21] are based on molecular self-assembled systems. In addition, the crystal packing adopted by p-conjugatedc ompounds determines their electronic andp hotophysicalp roperties and their later use in light-emitting electronic devices, [1,14,15] chemiresistives ensors, [15,22] agricultural films, [23] among others.…”

Section: Introductionmentioning

confidence: 99%

Understanding the Driving Mechanisms of Enhanced Luminescence Emission of Oligo(styryl)benzenes and Tri(styryl)‐s‐triazine

Domínguez

Moral

Fernández‐Liencres

et al. 2020

Chemistry A European J

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This work is focused on unraveling the mechanisms responsible for the aggregation‐induced enhanced emission and solid‐state luminescence enhancement effects observed in star‐shaped molecules based on 1,3,5‐tris(styryl)benzene and tri(styryl)‐s‐triazine cores. To achieve this, the photophysical properties of this set of molecules were analyzed in three states: free molecules, molecular aggregates in solution, and the solid state. Different spectroscopy and microscopy experiments and DFT calculations were conducted to scrutinize the causative mechanisms of the luminescence enhancement phenomenon observed in some experimental conditions. Enhanced luminescence emission was interpreted in the context of short‐ and long‐range excitonic coupling mechanisms and the restriction of intramolecular vibrations. Additionally, we found that the formation of π‐stacking aggregates could block E/Z photoisomerization through torsional motions between phenylene rings in the excited state, and hence, enhancing the luminescence of the system.

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“…Agarose gel electrophoresis was performed as previously described [21]. The dendron/siRNA complexes were prepared at increasing dendron/siRNA molar ratios and incubated for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes

et al. 2016

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Glioblastomas are the most common malignant primary brain tumours in adults and one of the most aggressive and difficult-to-treat cancers. No effective treatment exits actually for this tumour and new therapeutic approaches are needed for this disease. One possible innovative approach involves the nanoparticle-mediated specific delivery of drugs and/or genetic material to glioblastoma cells where they can provide therapeutic benefits. In the present work, we have synthesised and characterised several second generation amphiphilic polylysine dendrons to be used as siRNA carriers. We have found that, in addition to their siRNA binding properties, these new compounds inhibit the proliferation of two glioblastoma cell lines while being nontoxic for non-tumoural central nervous system cells like neurons and glia, cell types that share the anatomical space with glioblastoma cells during the course of the disease. The selective toxicity of these nanoparticles to glioblastoma cells, as compared to neurons and glial cells, involves mitochondrial depolarisation and reactive oxygen species production. This selective toxicity, together with the ability to complex and release siRNA, suggests that these new polylysine dendrons might offer a scaffold in the development of future nanoparticles designed to restrict the proliferation of glioblastoma cells.

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Efficient, Non-Toxic Hybrid PPV-PAMAM Dendrimer as a Gene Carrier for Neuronal Cells

Cited by 52 publications

References 58 publications

Cofilin activation mediates Bax translocation to mitochondria during excitotoxic neuronal death

Cofilin activation mediates Bax translocation to mitochondria during excitotoxic neuronal death

Understanding the Driving Mechanisms of Enhanced Luminescence Emission of Oligo(styryl)benzenes and Tri(styryl)‐s‐triazine

Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes

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