Divalent Cations: A Molecular Glue for Protein Materials

López‐Laguna, Hèctor; Sánchez, Julieta M.; Unzueta, Ugutz; Mangues, Ramón; Vázquez, Esther; Villaverde, Antonio

doi:10.1016/j.tibs.2020.08.003

Cited by 42 publications

(61 citation statements)

References 90 publications

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“…An optimized EPI-X4 tandem version with higher receptor affinity and serum stability [25] was genetically fused at the N-terminal of an H6-tagged GFP. As expected, the combination of a cationic peptide at amino terminus plus the polyhistidine (H6) carboxy terminal promoted protein assembling in NPs ranging from 10 to 80 nm in size, probably stabilized by divalent cation coordination through histidine-rich regions [30,31]. This size range is ideal for improving enhanced permeability and retention (EPR) effect and cell uptake, but also to minimize renal filtration (kidney cut-off around 6-8 nm) of any associated small molecular weight drugs [32].…”

Section: Resultssupporting

confidence: 55%

Biparatopic Protein Nanoparticles for the Precision Therapy of CXCR4+ Cancers

Cano‐Garrido

Álamo

Sánchez‐García

et al. 2021

Cancers

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The accumulated molecular knowledge about human cancer enables the identification of multiple cell surface markers as highly specific therapeutic targets. A proper tumor targeting could significantly avoid drug exposure of healthy cells, minimizing side effects, but it is also expected to increase the therapeutic index. Specifically, colorectal cancer has a particularly poor prognosis in late stages, being drug targeting an appropriate strategy to substantially improve the therapeutic efficacy. In this study, we have explored the potential of the human albumin-derived peptide, EPI-X4, as a suitable ligand to target colorectal cancer via the cell surface protein CXCR4, a chemokine receptor overexpressed in cancer stem cells. To explore the potential use of this ligand, self-assembling protein nanoparticles have been generated displaying an engineered EPI-X4 version, which conferred a modest CXCR4 targeting and fast and high level of cell apoptosis in tumor CXCR4+ cells, in vitro and in vivo. In addition, when EPI-X4-based building blocks are combined with biologically inert polypeptides containing the CXCR4 ligand T22, the resulting biparatopic nanoparticles show a dramatically improved biodistribution in mouse models of CXCR4+ human cancer, faster cell internalization and enhanced target cell death when compared to the version based on a single ligand. The generation of biparatopic materials opens exciting possibilities in oncotherapies based on high precision drug delivery based on the receptor CXCR4.

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Section: Resultssupporting

confidence: 55%

Biparatopic Protein Nanoparticles for the Precision Therapy of CXCR4+ Cancers

Cano‐Garrido

Álamo

Sánchez‐García

et al. 2021

Cancers

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“…Over time, much effort has been made to develop nanomaterials containing bivalent cations for various uses in medicine, biology, chemistry, and cosmetics [ 32 , 33 , 34 ]. Although their particularities have been obviously revealed by size, zeta potential, and chemical composition, their degree of entrapping the drugs, biocompatibility, and toxicity in laboratory animals are still not well established [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of the In Vivo Release and Biocompatibility of Novel Vesicles Containing Zinc in Rats

et al. 2021

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This paper is focused on the in vivo release and biocompatibility evaluation in rats of some novel systems entrapping zinc chloride in lipid vesicles. The particles were prepared by zinc chloride immobilization inside lipid vesicles made using phosphatidylcholine, stabilized with 0.5% chitosan solution, and dialyzed for 10 h to achieve a neutral pH. The submicrometric systems were physico-chemically characterized. White Wistar rats, assigned into four groups of six animals each, were treated orally with a single dose, as follows: Group I (control): deionized water 0.3 mL/100 g body weight; Group II (Zn): 2 mg/kg body weight (kbw) zinc chloride; Group III (LV-Zn): 2 mg/kbw zinc chloride in vesicles; Group IV (LVC-Zn): 2 mg/kbw zinc chloride in vesicles stabilized with chitosan. Haematological, biochemical, and immune parameters were assessed after 24 h and 7 days, and then liver fragments were collected for histopathological examination. The use of zinc submicrometric particles—especially those stabilized with chitosan—showed a delayed zinc release in rats. No substantial changes to blood parameters, plasma biochemical tests, serum complement activity, or peripheral neutrophils phagocytic capacity were noted; moreover, the tested substances did not induce liver architectural disturbances. The obtained systems provided a delayed release of zinc, and showed good biocompatibility in rats.

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“…Architectonically stable protein stages are depicted down below each picture. More details about the organization of final and intermediate materials can be found elsewhere (López-Laguna et al., 2021 ). (B) Methodological procedure of secretory granules displaying different types of divalent cations and concentrations.…”

Section: Methodsmentioning

confidence: 99%

“…Such methodologies involve a non-drug-containing material that increases the complexity of the system and the fabrication process, often imposing chemical constraints and toxicological concerns (Sharma et al., 2012 ; Palombo et al., 2014 ; Aragao-Santiago et al., 2016 ; Shen et al., 2017 ). Recently, self-contained, self-disintegrating protein material in form of microparticles have been developed (Chen et al., 2020 ; Sánchez et al., 2020 ), suited for a slow protein release in vivo (Sánchez et al., 2020 ; Serna et al., 2020 ; López-Laguna et al., 2021 ). These artificial structures mimic the molecular organization and functionality of the secretory granules from the mammalian endocrine system, which contain and release peptidic hormones to the bloodstream (Maji et al., 2009 ; Mankar et al., 2011 ; Jacob et al., 2016 ; Jacob et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%