A custom-made functionalization method to control the biological identity of nanomaterials

Padín-González, Esperanza; Navarro-Palomares, Elena; Valdivia, Lourdes; Iturrioz-Rodríguez, Nerea; Correa, Miguel Angel; Valiente, Rafael; Fanarraga, Mónica L.

doi:10.1016/j.nano.2020.102268

Cited by 9 publications

(16 citation statements)

References 41 publications

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“…2,4,5 Characterisation of the corona informs estimates of dissolution kinetics in environmentally relevant matrices, 4 increases accuracy of models for the environmental transport and fate of ENMs, 4,6 and enhances conclusions of ecotoxicity studies. 2 In parallel to the biomedical grand challenge of designing ENMs that acquire customised protein coronas to increase efficacy of nanopharmaceuticals, 7 characterisation of the environmentally formed corona informs design of ENMs with enhanced control and sustainability in environmental applications, including remediation, biofouling, and agriculture. For example, the protein corona mediates ENM uptake and fate in plants.…”

Section: Take Down Policymentioning

confidence: 99%

Environmental dimensions of the protein corona

et al. 2021

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The adsorption of biomolecules to the surface of engineered nanomaterials, known as corona formation, defines their biological identity by altering their surface properties and transforming the physical, chemical, and biological characteristics of the particles. In the first decade since the term protein corona was coined, studies have focused primarily on biomedical applications and human toxicity. The relevance of the environmental dimensions of the protein corona are still emerging. Often referred to as the eco-corona, a biomolecular coating forms upon nanomaterials as they enter the environment and may include proteins, as well as a diverse array of other biomolecules such as metabolites from cellular activity and/or natural organic matter. Proteins remain central in studies of eco-coronas because of the ease of monitoring and structurally characterising proteins, as well as their crucial role in receptor engagement and signaling. The proteins within the eco-corona are optimal targets to establish the biophysicochemical principles of corona formation and transformation, as well as downstream impacts on nanomaterial uptake, distribution, and impacts on the environment. Moreover, proteins appear to impart a biological identity leading to cellular or organismal recognition of nanomaterials, a unique characteristic in comparison to natural organic matter. We contrast insights into protein corona formation from clinical samples with those in environmentally relevant systems. Principles specific to the environment are also explored to gain insights into dynamics of interaction with / exchange by other biomolecules, including changes during trophic transfer and ecotoxicity. With many challenges remaining, we also highlight key opportunities for method development and impactful systems on which to focus the next phase of eco-corona studies. By interrogating these environmental dimensions of the protein corona, we offer a perspective on how mechanistic insights into protein coronas in the environment can lead to more sustainable, environmentally safe nanomaterials, as well as enhance the efficacy of nanomaterials used in remediation and in the agri-sector.

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Section: Take Down Policymentioning

confidence: 99%

Environmental dimensions of the protein corona

et al. 2021

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“…Here we use biotechnology to produce a new synthetic protein containing a single “B” subunit of the Shiga toxin (that we named ShTxB), genetically attached to a cationic peptide (6xHis-tag) to electrostatically functionalized nanomaterials following a method we have previously described and characterized ( Figure S3 ) [ 37 ]. This peptidic cationic tail creates an electrostatic zipper with the negative surface of the particles that allows oriented positioning of the ShTxB ligand on the nanoparticle surface ( Figure 2 a).…”

Section: Resultsmentioning

confidence: 99%

“…This peptidic cationic tail creates an electrostatic zipper with the negative surface of the particles that allows oriented positioning of the ShTxB ligand on the nanoparticle surface ( Figure 2 a). Moreover, the binding method is highly stable upon exposure to physiological conditions (for times longer than 72 h) and significantly hinders non-specific protein biofouling [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

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Targeting Nanomaterials to Head and Neck Cancer Cells Using a Fragment of the Shiga Toxin as a Potent Natural Ligand

Navarro-Palomares

García‐Hevia

Padín-González

et al. 2021

Cancers

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Head and Neck Cancer (HNC) is the seventh most common cancer worldwide with a 5-year survival from diagnosis of 50%. Currently, HNC is diagnosed by a physical examination followed by an histological biopsy, with surgery being the primary treatment. Here, we propose the use of targeted nanotechnology in support of existing diagnostic and therapeutic tools to prevent recurrences of tumors with poorly defined or surgically inaccessible margins. We have designed an innocuous ligand-protein, based on the receptor-binding domain of the Shiga toxin (ShTxB), that specifically drives nanoparticles to HNC cells bearing the globotriaosylceramide receptor on their surfaces. Microscopy images show how, upon binding to the receptor, the ShTxB-coated nanoparticles cause the clustering of the globotriaosylceramide receptors, the protrusion of filopodia, and rippling of the membrane, ultimately allowing the penetration of the ShTxB nanoparticles directly into the cell cytoplasm, thus triggering a biomimetic cellular response indistinguishable from that triggered by the full-length Shiga toxin. This functionalization strategy is a clear example of how some toxin fragments can be used as natural biosensors for the detection of some localized cancers and to target nanomedicines to HNC lesions.

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“…This receptor is overexpressed on the surface of multiple tumor cell types including breast [ 50 , 51 ], ovarian [ 52 ], lung [ 53 ], stomach, oral cancers [ 54 ] and, its relatively low expression on normal tissues makes it a clinically useful molecular target for directed therapies. The synthetic protein sequence designed contained: (i) a cationic CNT-binding peptide [ 55 ] in the N-terminus, (ii) a fluorescent reporting protein (GFP), and (iii) a the HER2-binding peptide [ 56 ] at the C-terminus (Fig. 7 a).…”

Section: Resultsmentioning

confidence: 99%

The unpredictable carbon nanotube biocorona and a functionalization method to prevent protein biofouling

et al. 2021

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Background The intrinsic physicochemical properties of carbon nanotubes (CNTs) make them unique tools in nanotechnology. Their elemental composition, resilience, thermal properties, and surface reactivity make CNTs also of undisputed interest in biotechnology. In particular, their extraordinary ability to capture biomolecules on their surface makes them essential in this field. The proteins adsorbed on the CNTs create a biological coating that endows them the ability to interact with some cell receptors, penetrate membranes or interfere with cell biomechanics, thus behaving as an active bio-camouflage. But some of these proteins unfold, triggering an immune response that unpredictably changes the biological activity of CNTs. For this reason, the control of the biocorona is fundamental in the nanobiotechnology of CNTs. Results Using TEM and AFM here we demonstrate a significant increase in CNTs diameter after protein functionalization. A quantitative analysis using TGA revealed that between 20 and 60% of the mass of functionalized nanotubes corresponds to protein, with single-walled CNTs capturing the highest amounts. To qualitatively/quantitatively characterize these biocoatings, we studied the biochemical "landscape" of the proteins captured by the different nanotubes after functionalization under various conditions. This study revealed a significant variability of the proteins in the corona as a function of the type of nanotube, the functionalization temperature, or the time after exposure to serum. Remarkably, the functionalization of a single type of CNT with sera from various human donors also resulted in different protein landscapes. Given the unpredictable assortment of proteins captured by the corona and the biological implications of this biocoating, we finally designed a method to genetically engineer and produce proteins to functionalize nanotubes in a controlled and customizable way. Conclusions We demonstrate the high unpredictability of the spontaneous protein corona on CNTs and propose a versatile functionalization technique that prevents the binding of nonspecific proteins to the nanotube to improve the use of CNTs in biomedical applications.

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A custom-made functionalization method to control the biological identity of nanomaterials

Cited by 9 publications

References 41 publications

Environmental dimensions of the protein corona

Environmental dimensions of the protein corona

Targeting Nanomaterials to Head and Neck Cancer Cells Using a Fragment of the Shiga Toxin as a Potent Natural Ligand

The unpredictable carbon nanotube biocorona and a functionalization method to prevent protein biofouling

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