Superoxide Dismutase Enzymosomes: Carrier Capacity Optimization, in Vivo Behaviour and Therapeutic Activity

Corvo, M. Luísa; Marinho, H. Susana; Marcelino, Paulo; Lopes, Rodrigo J.G.; Vale, Carlos; Marques, Claúdia R.; Martins, Luísa; Laverman, Peter; Storm, Gert; Martins, M.B.F.

doi:10.1007/s11095-014-1447-7

Cited by 33 publications

(41 citation statements)

References 33 publications

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“…However, mitochondria also prevent ROS and regulate the steady-state concentration of O2 •− in the intermembrane space by three different mechanisms. The first mechanism involves the enzyme superoxide dismutase (SOD) ( 39 ), acting through the dismutation of O 2 and producing hydrogen peroxide (H2) in fully reduced water product. There are two types of SOD including the specific mitochondrial matrix containing the manganese active site ( 40 ) (MnSOD or SOD2), which eliminates O2 •− formed in the matrix or on the inner side of the inner membrane, and SOD containing copper and zinc ( 41 ) instead of manganese SOD (copper-zinc SOD or SOD1) located in the cytoplasm of eukaryotic cells.…”

Section: Oxidative Stressmentioning

confidence: 99%

Role of oxidative stress in Alzheimer's disease

2016

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Alzheimer's disease (AD) is the most common cause of disability in individuals aged >65 years worldwide. AD is characterized by the abnormal deposition of amyloid β (Aβ) peptide, and intracellular accumulation of neurofibrillary tangles of hyperphosphorylated τ protein and dementia. The neurotoxic oligomer Aβ peptide, which is the neuropathological diagnostic criterion of the disease, together with τ protein, are mediators of the neurodegeneration that is among the main causative factors. However, these phenomena are mainly initiated and enhanced by oxidative stress, a process referring to an imbalance between antioxidants and oxidants in favour of oxidants. This imbalance can occur as a result of increased free radicals or a decrease in antioxidant defense, free radicals being a species that contains one or more unpaired electrons in its outer shell. The major source of potent free radicals is the reduction of molecular oxygen in water, that initially yields the superoxide radical, which produces hydrogen peroxide by the addition of an electron. The reduction of hydrogen peroxide produces highly reactive hydroxyl radicals, termed reactive oxygen species (ROS) that can react with lipids, proteins, nucleic acids, and other molecules and may also alter their structures and functions. Thus, tissues and organs, particularly the brain, a vulnerable organ, are affected by ROS due to its composition. The brain is largely composed of easily oxidizable lipids while featuring a high oxygen consumption rate. The current review examined the role of oxidative stress in AD.

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Section: Oxidative Stressmentioning

confidence: 99%

Role of oxidative stress in Alzheimer's disease

2016

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“…It was previously reported that the FITC, UCU and CAT molecules competitively interacted with the interfacial regions of zwitterionic enzymosomal membranes through electrostatic and hydrophobic interactions 9 34 . Corvo et al 35 recently reported that superoxide dismutase (SOD) could covalently attach to the outer surfaces of enzymosomes, and this type of enzymosomes showed earlier therapeutic activities than did both free SOD and another type of enzymosomes with SOD encapsulated in the aqueous interior. The UCU molecules existed in the ESU or ESUC in three ways: (1) The UCU or UCU in the presence of CAT was attached the outer surface of ESU or ESUC, which in clinical practice might, enable rapid enzyme efficacy for patients; (2) The UCU or UCU in the presence of CAT was attached the inner surface of ESU or ESUC; and (3) the UCU or UCU in the presence of CAT was just entrapped inside the ESU or ESUC without attaching to the inner surfaces of membranes.…”

Section: Resultsmentioning

confidence: 99%

Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes

Zhou

Zhang

et al. 2016

Sci Rep

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Enzyme therapy is an effective strategy to treat diseases. Three strategies were pursued to provide the favorable microenvironments for uricase (UCU) to eventually improve its features: using the right type of buffer to constitute the liquid media where catalyze reactions take place; entrapping UCU inside the selectively permeable lipid vesicle membranes; and entrapping catalase together with UCU inside the membranes. The nanosized alkaline enzymosomes containing UCU/(UCU and catalase) (ESU/ESUC) in bicine buffer had better thermal, hypothermal, acid-base and proteolytic stabilities, in vitro and in vivo kinetic characteristics, and uric acid lowering effects. The favorable microenvironments were conducive to the establishment of the enzymosomes with superior properties. It was the first time that two therapeutic enzymes were simultaneously entrapped into one enzymosome having the right type of buffer to achieve added treatment efficacy. The development of ESU/ESUC in bicine buffer provides valuable tactics in hypouricemic therapy and enzymosomal application.

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“…Recently, the same liposome with antioxidant enzyme superoxide dismutase covalently linked to the distal end of DSPE-PEG showed an enhanced therapeutic result in the IRI. 18 This opens the possibility to access diagnostic and therapy with the same nanoplatform.…”

Section: Magnetoliposomesmentioning

confidence: 99%

Development of New Contrast Agents for Imaging Function and Metabolism by Magnetic Resonance Imaging

Carvalho¹,

Gonçalves

Corvo

et al. 2017

Magn Reson�Insights

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Liposomes are interesting nanosystems with a wide range of medical application. One particular application is their ability to enhance contrast in magnetic resonance images; when properly loaded with magnetic/superparamagnetic nanoparticles, this means to act as contrast agents. The design of liposomes loaded with magnetic particles, magnetoliposomes, presents a large number of possibilities depending on the application from image function to metabolism. More interesting is its double function application as theranostics (diagnostics and therapy). The synthesis, characterization, and possible medical applications of two types of magnetoliposomes are reviewed. Their performance will be compared, in particular, their efficiency as contrast agents for magnetic resonance imaging, measured by their relaxivities r1 and r2 relating to their particular composition. One of the magnetoliposomes had 1,2-diacyl-sn-glycero-3-phosphocholine (soy) as the main phospholipid component, with and without cholesterol, varying its phospholipid to cholesterol molar ratios. The other formulation is a long-circulating liposome composed of 1,2-diacyl-sn-glycero-3-phosphocholine (egg), cholesterol, and 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]. Both nanosystems were loaded with superparamagnetic iron oxide nanoparticles with different sizes and coatings.

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Superoxide Dismutase Enzymosomes: Carrier Capacity Optimization, in Vivo Behaviour and Therapeutic Activity

Abstract: SOD-enzymosomes were shown to be a new and successful therapeutic approach to oxidative stress-associated inflammatory situations/diseases.

Cited by 33 publications

References 33 publications

Role of oxidative stress in Alzheimer's disease

Role of oxidative stress in Alzheimer's disease

Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes

Development of New Contrast Agents for Imaging Function and Metabolism by Magnetic Resonance Imaging

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