New Synthesis and Biodistribution of the D-Amino Acid Oxidase-Magnetic Nanoparticle System

Cappellini, Francesca; Recordati, Camilla; Maglie, Marcella De; Pollegioni, Loredano; Rossi, Federica; Daturi, Marco; Gornati, Rosalba; Bernardini, Giovanni

doi:10.4155/fso.15.67

Cited by 11 publications

(13 citation statements)

References 33 publications

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“…Moreover, cobalt NPs are magnetic and this property allows to manipulate them in a chemical or biological system using an external magnet. Moreover, magnetic NPs can be easily conjugated to biologically important constituents such as DNA, peptides, antibodies 24 as well as enzymes 25 26 and sugars 27 28 to construct versatile bio-nano hybrids.…”

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Cobalt oxide nanoparticles can enter inside the cells by crossing plasma membranes

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Gornati

et al. 2016

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The ability of nanoparticles (NPs) to be promptly uptaken by the cells makes them both dangerous and useful to human health. It was recently postulated that some NPs might cross the plasma membrane also by a non-endocytotic pathway gaining access to the cytoplasm. To this aim, after having filled mature Xenopus oocytes with Calcein, whose fluorescence is strongly quenched by divalent metal ions, we have exposed them to different cobalt NPs quantifying quenching as evidence of the increase of the concentration of Co2+ released by the NPs that entered into the cytoplasm. We demonstrated that cobalt oxide NPs, but not cobalt nor cobalt oxide NPs that were surrounded by a protein corona, can indeed cross plasma membranes.

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Cobalt oxide nanoparticles can enter inside the cells by crossing plasma membranes

Bossi

Zanella

Gornati

et al. 2016

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“…Since the specic activity of the RgDAAO stock solution was 59 U mg À1 , we estimated up to 24 U per mg of NP-APTES. The NPs here synthesized showed a smaller diameter compared to the ones used by Cappellini et al 24 and this allowed a 7 fold increase of the DAAO/NP (w/w) ratio.…”

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“…That resulted in an increased cellular internalization of the enzyme, a prolonged enzymatic activity and storage stability, and the possibility of targeting to the cancer mass with the help of an external magnetic eld. However, while the APTES functionalization represents a good amino group donor, its activation via glutaraldehyde can affect the enzyme integrity 21 leading to a loss of DAAO activity.22,23 Cappellini et al 24 reported a higher yield for the NP-DAAO synthesis when conducted via EDC/NHS instead of with glutaraldehyde. Furthermore, also the NP diameter and aggregation inuence the amount of loaded enzyme.…”

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“…The amount of stock DAAO used for the conjugation to NP-APTES has been chosen starting from the ratio of mg of DAAO per NP-APTES surface area (calculated from the average particle diameter, assuming spherical particles) used by Cappellini et al 24 and then moving to DAAO saturation per NP-APTES. For one mg of NP-APTES particles up to 446 mg of RgDAAO was bound (Fig.…”

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Synthesis, characterization and programmable toxicity of iron oxide nanoparticles conjugated withd-amino acid oxidase

et al. 2017

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ad D-amino acid oxidase (DAAO) is an enzyme which generates reactive oxygen species (ROS) and it is believed to have potential uses as a novel therapeutic molecule if internalized by cancer cells or if they are localized close to their plasma membrane. When conjugated onto iron oxide nanoparticles (NPs), the enzyme can be magnetically directed to targeted locations with an increased efficacy. A subsequent injection of DAAO substrate D-alanine can initiate ROS production and induce apoptosis of cells surrounding the NP-DAAO complex. Here, we describe a platform for optimal bioconjugation using monodisperse g-Fe 2 O 3 NPs ($10 nm) resulting in high DAAO loading, stable NP-DAAO dispersions and more than 90% enzymatic activity recovery, which is retained using the particles in human serum. Lastly, since the NP-DAAO system is designed for cancer therapy, we proved its efficacy in killing SKOV-3, U87 and HCT-116 cancer cells.Nanobiotechnology has found widespread applications 1 in biomedicine as diagnostic imaging tools, 2,3 drug delivery systems, 4,5 vaccines 6,7 and in immunotherapy. 8 NPs can be employed to produce a great variety of bioconjugates by graing biomolecules onto a NP carrier. In oncology, for example, recent studies have shown that engineered NPs are capable of reaching specic targeted areas of the body and of releasing the therapeutic drug locally.9-12 This novel approach has the potential to increase the drug efficacy and to eliminate the side effects. 13To guide the bioconjugates through the body, one can use magnetic NPs that, aer intravenous administration, can be directed to the cancerous tissue with an external magnetic eld.14 Magnetic NPs alone are used as an effective anticancer agent during hyperthermic therapy in which NPs exposed to an alternating magnetic eld produce heat that kills all the surrounding cells. 15-19D-Amino acid oxidase from Rhodotorula gracilis (RgDAAO, EC 1.4.3.3) is a avoenzyme that utilizes D-amino acids to produce reactive oxygen species (ROS) 20 and can be used to induce apoptosis. In particular the co-administration with D-alanine as substrate, gives the corresponding a-keto acid, ammonia and H 2 O 2 . Despite the benet in using this enzyme in therapeutic applications, the main limitations are the low enzyme stability, the low efficacy in cellular internalization and the lack of specic molecular targeting. To overcome these limitations, in the past few years different attempts have been made in the development of NP-DAAO systems where the enzyme was covalently bound to the amino groups of APTES functionalized NPs. That resulted in an increased cellular internalization of the enzyme, a prolonged enzymatic activity and storage stability, and the possibility of targeting to the cancer mass with the help of an external magnetic eld. However, while the APTES functionalization represents a good amino group donor, its activation via glutaraldehyde can affect the enzyme integrity 21 leading to a loss of DAAO activity.22,23 Cappellini et al. 24 reported a higher yield...

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“…Considering the various applications described above, iron-based NPs raise concerns for the potential risk of exposure through ingestion, which can occurs both into the aquatic environment, this being the ultimate recipient of NPs that are intentionally or accidentally spilled into it, and when they are used as nanoingredients. In vitro (Gornati et al 2016;Coccini et al 2019) and in vivo experiments on mammals (Cappellini et al 2015;Feng et al 2018) have been performed to evaluate iron NP toxicity. Moreover, several iron NPs (i.e.…”

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Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles

et al. 2019

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Iron nanoparticles (NPs) have been proposed as a tool in very different fields such as environmental remediation and biomedical applications, including food fortification against iron deficiency, even if there is still concern about their safety. Here, we propose Xenopus laevis embryos as a suitable model to investigate the toxicity and the bio-interactions at the intestinal barrier of Fe 3 O 4 and zerovalent iron (ZVI) NPs compared to Fe(II) and (III) salts in the 5 to 100 mg Fe/L concentration range using the Frog Embryo Teratogenesis Assay in Xenopus (FETAX). Our results demonstrated that, at concentrations at which iron salts induce adverse effects, both iron NPs do not cause acute toxicity or teratogenicity even if they accumulate massively in the embryo gut. Prussian blue staining, confocal and electron microscopy allowed mapping of iron NPs in enterocytes, along the paracellular spaces and at the level of the basement membrane of a well-preserved intestinal epithelium. Furthermore, the high bioaccumulation factor and the increase in embryo length after exposure to iron NPs suggest greater iron intake, an essential element for organisms. Together, these results improve the knowledge on the safety of orally ingested iron NPs and their interaction with the intestinal barrier, useful for defining the potential risks associated with their use in food/feed fortification.

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New Synthesis and Biodistribution of the D-Amino Acid Oxidase-Magnetic Nanoparticle System

Cited by 11 publications

References 33 publications

Cobalt oxide nanoparticles can enter inside the cells by crossing plasma membranes

Cobalt oxide nanoparticles can enter inside the cells by crossing plasma membranes

Synthesis, characterization and programmable toxicity of iron oxide nanoparticles conjugated withd-amino acid oxidase

Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles

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