Antiviral Properties of Polymeric Aziridine- and Biguanide-Modified Core–Shell Magnetic Nanoparticles

Bromberg, Lev; Bromberg, Daniel J.; Hatton, T. Alan; Bandı́n, Isabel; Concheiro, Angel; Alvarez‐Lorenzo, Carmen

doi:10.1021/la205127x

Cited by 36 publications

(26 citation statements)

References 68 publications

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“…Virucidal molecules cause irreversible viral deactivation, indeed their effect is retained even if dilution occurs after the initial interaction with the virus. 22 There is a vast literature on many virucidal materials ranging from simple detergents, to strong acids, or more refined polymers, 23 and nanoparticles (NPs) [24][25][26][27] that, in some cases, are capable of releasing ions. 28,29 In all cases, the approaches utilized have intrinsic cellular toxicity.…”

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confidence: 99%

Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

et al. 2017

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Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

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confidence: 99%

Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

et al. 2017

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“…Modified PEIs were also evaluated by Alvarez-Lorenzo et al synthesizing modified PEI by polymerization of aziridine and magnetite-silica core-shell particles. It was evident that these polymers inhibited bacteriophage MS2, HSV-1, enveloped viral hemorrhagic septicaemia viruses (VHSV), and nonenveloped infectious pancreatic necrosis virus (IPNV) [97]. oxide (Cu2O), sulphide (Cu2S), iodide (CuI), and chloride (CuCl) have high antiviral efficiency, compared to solid-state silver and cupric compounds [22].…”

Section: Amines Containing-polymers and Polycationsmentioning

confidence: 99%

Polymers in the Medical Antiviral Front-Line

2020

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Antiviral polymers are part of a major campaign led by the scientific community in recent years. Facing this most demanding of campaigns, two main approaches have been undertaken by scientists. First, the classic approach involves the development of relatively small molecules having antiviral properties to serve as drugs. The other approach involves searching for polymers with antiviral properties to be used as prescription medications or viral spread prevention measures. This second approach took two distinct directions. The first, using polymers as antiviral drug-delivery systems, taking advantage of their biodegradable properties. The second, using polymers with antiviral properties for on-contact virus elimination, which will be the focus of this review. Anti-viral polymers are obtained by either the addition of small antiviral molecules (such as metal ions) to obtain ion-containing polymers with antiviral properties or the use of polymers composed of an organic backbone and electrically charged moieties like polyanions, such as carboxylate containing polymers, or polycations such as quaternary ammonium containing polymers. Other approaches include moieties hybridized by sulphates, carboxylic acids, or amines and/or combining repeating units with a similar chemical structure to common antiviral drugs. Furthermore, elevated temperatures appear to increase the anti-viral effect of ions and other functional moieties.

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“…This antiviral activity relies on surface modification with sulfonates or other molecules. Bromberg et al (2012) synthesized core-shell silica-magnetic NPs functionalized with poly(hexamethylene biguanide) (PHMBG). The authors reported that NPs exhibited a notable virucidal effect on several virus strains, which occurred via amino alkylation of their genomic materials, blocking genome replication and leading to viral inactivation (Bromberg et al, 2012).…”

Section: Iron Oxide Nanoparticlesmentioning

confidence: 99%