Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury

Nukolova, N. V.; Aleksashkin, A.D.; Abakumova, Tatiana O.; Morozova, Аnna; Gubskiy, Ilya; Kirzhanova, Ekaterina A.; Abakumov, Maxim; Chekhonin, V. P.; Klyachko, Natalia L.; Kabanov, Alexander V.

doi:10.1016/j.jconrel.2017.11.044

Cited by 54 publications

(30 citation statements)

References 27 publications

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“…The decrease of D m /D HD from 1/5 to 1/6 lead to the frequency shift from 210 to 120 Hz 33 . Assuming similar dependence of the peak frequency on the D m /D HD , the critical frequency of our system which consists of The antioxidant polyion complexes of SOD1 with PLL-PEG have shown recovery improvement in the models of ischemic brain injury and spinal cord injury 34,35 . However, due to the narrow time window for antioxidant enzymes to work in the acute phase of diseases and mitigate the oxidative stress, it is essential to use formulations with high catalytic activity and rapid enzyme release.…”

Section: Discussionmentioning

confidence: 85%

Enzyme Release from Polyion Complex by Extremely Low Frequency Magnetic Field

Vlasova

Vishwasrao

Abakumov

et al. 2020

Sci Rep

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Remote nano-magneto-mechanical actuation of magnetic nanoparticles (Mnps) by non-heating extremely low frequency magnetic field (ELF MF) is explored as a tool for non-invasive modificationof bionanomaterials in pharmaceutical and medical applications. Here we study the effects of ELF MF (30-160 Hz, 8-120 kA/m) on the activity and release of a model enzyme, superoxide dismutase 1 (SOD1) immobilized by polyion coupling on dispersed Mnps aggregates coated with poly(L-lysine)-blockpoly(ethylene glycol) block copolymer (s-MNPs). Such fields do not cause any considerable heating of Mnps but promote their rotating-oscillating mechanical motion that produces mechanical forces and deformations in adjacent materials. We observed the changes in the catalytic activity of immobilized SOD1 as well as its release from the s-MNPs/SOD1 polyion complex upon application of the ELF MF for 5 to 15 min. At longer exposures (25 min) the s-MNPs/SOD1 dispersion destabilizes. The bell-shaped effect of the field frequency with maximum at f = 50 Hz and saturation effect of field strength (between 30 kA/m and 120 kA/m at f = 50 Hz) are reported and explained. The findings are significant as one early indication of the nano-magneto-mechanical disruption by eLf Mf of cooperative polyion complexes that are widely used for design of current functional healthcare bionanomaterials.Non-invasive functional control of bionanomaterials in inaccessible areas of a human body (e.g., biochemical reactions, drug release, gene expression, etc.) could greatly advance development of diagnostics and therapeutic modalities 1 . This control can be accomplished by remote actuation of nanoparticles by external fields 2-6 . In recent years magnetic nanoparticles (MNPs) have been investigated for cell separation, targeted drug delivery, and magnetic resonance imaging (MRI) 7-9 . Remote actuation of MNPs by radio frequency (200-800 kHz) magnetic fields has been used in hyperthermia for cancer therapy 10-12 . However, this approach has a risk of tissue overheating and damage. Recently an alternative nano-magneto-mechanical actuation of MNPs by non-heating extremely low frequency magnetic field (ELF MF) has attracted increasing attention in drug delivery and nanomedicine [13][14][15][16][17] .The phenomenon of nano-magneto-mechanical actuation is linked to the ability of MNPs to undergo mechanical motion in ELF MF and as a consequence produce mechanical forces and deformations in adjacent materials. It is well known, that a single-domain MNPs can relax in an external magnetic field, reducing an angle between the MNPs magnetic moment μ and the field vector H [18][19][20] . Two basic types of relaxation phenomena are dependent on the size of the magnetic core. MNPs with D m less than some critical value d* experience rotation of magnetic moments μ towards the vector H, which proceeds mainly by overcoming the crystallographic anisotropy of the lattice, without causing significant mechanical motion of the particle (Néel relaxation). MNPs with a diameter D m greater than d*...

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Section: Discussionmentioning

confidence: 85%

Enzyme Release from Polyion Complex by Extremely Low Frequency Magnetic Field

Vlasova

Vishwasrao

Abakumov

et al. 2020

Sci Rep

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“…Such enzymes could be exploited as therapeutics to limit ROS-induced damage, such as cell death, mutations, chromosomal aberrations and carcinogenesis [60]. Among these enzymes, superoxide dismutases (SODs) have been already tested as therapeutics in several delivery systems, such as liposomes [61], mesoporous silica NPs [62], polyketal microparticles [63] and polyion complexes [64]. Indeed, SODs are a group of enzymes that contain metals and can dismute the superoxide anion (O2-) into hydrogen peroxide and molecular oxygen.…”

Section: Resultsmentioning

confidence: 99%

Nanocarriers for Protein Delivery to the Cytosol: Assessing the Endosomal Escape of Poly(Lactide-co-Glycolide)-Poly(Ethylene Imine) Nanoparticles

2019

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Therapeutic proteins and enzymes are a group of interesting candidates for the treatment of numerous diseases, but they often require a carrier to avoid degradation and rapid clearance in vivo. To this end, organic nanoparticles (NPs) represent an excellent choice due to their biocompatibility, and cross-linked enzyme aggregates (CLEAs)-loaded poly (lactide-co-glycolide) (PLGA) NPs have recently attracted attention as versatile tools for targeted enzyme delivery. However, PLGA NPs are taken up by cells via endocytosis and are typically trafficked into lysosomes, while many therapeutic proteins and enzymes should reach the cellular cytosol to perform their activity. Here, we designed a CLEAs-based system implemented with a cationic endosomal escape agent (poly(ethylene imine), PEI) to extend the use of CLEA NPs also to cytosolic enzymes. We demonstrated that our system can deliver protein payloads at cytoplasm level by two different mechanisms: Endosomal escape and direct translocation. Finally, we applied this system to the cytoplasmic delivery of a therapeutically relevant enzyme (superoxide dismutase, SOD) in vitro.

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“…It is well documented that ROS overproduction plays a vital role in the secondary injury cascade after acute TSCI. 20,23 To simulate the ROS-induced oxidative damage to cells, H 2 O 2 was added into the cell culture medium, 24 and apparent cell death was observed after 24 h of culture ( Figure 3A and Figure S8A). Then, the antioxidation effect of Se-CQDs was investigated in astrocytes and N2a cells upon treatment with 250 μM H 2 O 2 .…”

Section: Biocompatibility and Antioxidation Effect Of Se-cqdsmentioning

confidence: 99%

“…5,10,17 The over-produced ROS can cause severe lipid peroxidation, as well as oxidative damage to proteins and DNA, resulting in the degeneration and demyelination of nerve fibers and even apoptosis of neuronal cells in the injured site. [18][19][20][21][22] Moreover, the easy distribution of ROS into the neighboring area of the injured site often causes the expansion of the injured site, leading to aggravated secondary injury with more serious locomotion defects. 16,23 Therefore, the scavenging of ROS has been established to be an effective route to attenuate secondary injury in acute TSCI treatment.…”

Section: Introductionmentioning

confidence: 99%

“…16,23 Therefore, the scavenging of ROS has been established to be an effective route to attenuate secondary injury in acute TSCI treatment. 20,21,[23][24][25] In the present study, a type of selenium-doped carbon quantum dots (Se-CQDs) was prepared and used for effectively ameliorating secondary TSCI ( Figure 1). The Se-CQDs were prepared via a simple approach, ie, hydrothermal treatment of L-selenocystine.…”

Section: Introductionmentioning

confidence: 99%

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<p>Selenium-Doped Carbon Quantum Dots Efficiently Ameliorate Secondary Spinal Cord Injury via Scavenging Reactive Oxygen Species</p>

Luo¹,

Wang²,

Liu³

et al. 2020

IJN

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Background The excess production of reactive oxygen species (ROS) after traumatic spinal cord injury (TSCI) has been identified as a leading cause of secondary injury, which can significantly exacerbate acute damage in the injured spinal cord. Thus, scavenging of ROS has emerged as an effective route to ameliorate secondary spinal cord injury. Purpose Selenium-doped carbon quantum dots (Se-CQDs) with the ability to scavenge reactive oxygen species were prepared and used for efficiently ameliorating secondary injury in TSCI. Methods Water-soluble Se-CQDs were easily synthesized via hydrothermal treatment of l -selenocystine. The chemical structure, size, and morphology of the Se-CQDs were characterized in detail. The biocompatibility and protective effects of the Se-CQDs against H 2 O 2 -induced oxidative damage were investigated in vitro. Moreover, the behavioral test, bladder function, histological observation, Western blot were used to investigate the neuroprotective effect of Se-CQDs in a rat model of contusion TSCI. Results The obtained Se-CQDs exhibited good biocompatibility and remarkable protective effect against H 2 O 2 -induced oxidative damage in astrocytes and PC12 cells. Moreover, Se-CQDs displayed marked anti-inﬂammatory and anti-apoptotic activities, which thereby reduced the formation of glial scars and increased the survival of neurons with unscathed myelin sheaths in vivo. As a result, Se-CQDs were capable of largely improving locomotor function of rats with TSCI. Conclusion This study suggests that Se-CQDs can be used as a promising therapeutic platform for ameliorating secondary injury in TSCI.

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Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury

Cited by 54 publications

References 27 publications

Enzyme Release from Polyion Complex by Extremely Low Frequency Magnetic Field

Enzyme Release from Polyion Complex by Extremely Low Frequency Magnetic Field

Nanocarriers for Protein Delivery to the Cytosol: Assessing the Endosomal Escape of Poly(Lactide-co-Glycolide)-Poly(Ethylene Imine) Nanoparticles

<p>Selenium-Doped Carbon Quantum Dots Efficiently Ameliorate Secondary Spinal Cord Injury via Scavenging Reactive Oxygen Species</p>

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