Dexamethasone Conjugation to Biodegradable Avidin-Nucleic-Acid-Nano-Assemblies Promotes Selective Liver Targeting and Improves Therapeutic Efficacy in an Autoimmune Hepatitis Murine Model

Violatto, Martina Bruna; Casarin, Elisabetta; Talamini, Laura; Russo, Luca; Baldan, Simone; Tondello, Camilla; Messmer, Marie C.; Hintermann, Edith; Rossi, Alessandro; Passoni, Alice; Bagnati, Renzo; Biffi, Stefania; Toffanin, Chiara; Fumagalli, Stefano; Simoni, Maria Grazia De; Barisani, Donatella; Salmona, Mario; Christen, Urs; Invernizzi, Pietro; Bigini, Paolo; Morpurgo, Margherita

doi:10.1021/acsnano.8b09655

Cited by 42 publications

(42 citation statements)

References 43 publications

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“…Therefore, antifibrotic agents are urgently needed, and they should preferentially act exclusively in the fibrotic milieu in order to prevent systemic side-effects [190][191][192][193][194]. In this regard, nanoparticles are an attractive tool, since they naturally accumulate predominantly in the liver [195,196]. Antifibrotic biopharmaceuticals, such as recombinant monoclonal antibodies, could target CAMs following three strategies: (A) CAMs which support homing of proinflammatory/profibrotic cell types will be blocked; (B) CAMs which show intrinsic profibrotic activity will be directly inhibited; or (C) CAMs will be used to target antifibrotic drugs to a specific cell type.…”

Section: Adhesion Molecules As Hepatic Fibrosis Markers and As Therapmentioning

confidence: 99%

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Hintermann

Christen

2019

Cells

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Fibrogenesis is a progressive scarring event resulting from disrupted regular wound healing due to repeated tissue injury and can end in organ failure, like in liver cirrhosis. The protagonists in this process, either liver-resident cells or patrolling leukocytes attracted to the site of tissue damage, interact with each other by soluble factors but also by direct cell–cell contact mediated by cell adhesion molecules. Since cell adhesion molecules also support binding to the extracellular matrix, they represent excellent biosensors, which allow cells to modulate their behavior based on changes in the surrounding microenvironment. In this review, we focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. We describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies.

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Section: Adhesion Molecules As Hepatic Fibrosis Markers and As Therapmentioning

confidence: 99%

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Hintermann

Christen

2019

Cells

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“…Microscopy techniques were adapted from protocols previously described (Violatto et al, 2019). Briefly, samples were acquired using Nikon A1 Confocal and Nikon N-SIM microscopes.…”

Section: Methodsmentioning

confidence: 99%

Super Resolution Microscopy of SUMO Proteins in Neurons

Colnaghi

Russo

Natale

et al. 2019

Front. Cell. Neurosci.

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The ubiquitously expressed SUMO proteins regulate a plethora of cellular pathways and processes. While they have a predominantly nuclear localization, extranuclear roles of SUMO isoforms at the synapse have also been described, making SUMOylation one of the major post-translational regulators of nerve functions. These findings have however recently been challenged, at least for SUMO1, by the analysis of knock-in mice expressing His6-HA-SUMO1, where the authors failed to detect the protein at the synapse. In the ongoing dispute, the subcellular distribution in neurons of SUMO2/3 and of the E2 SUMO ligase Ubc9 has not been examined. To investigate whether SUMO proteins do or do not localize at the synapse, we studied their localization in hippocampal primary neurons by super resolution microscopy. We found that SUMO1, SUMO2/3, and Ubc9 are primarily nuclear proteins, which also colocalize partially with pre- and post-synaptic markers such as synaptophysin and PSD95.

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“…These NPs were generated from a nucleic acid filament and avidin, a protein in egg whites. These NPs were designed to selectively deliver dexamethasone to the liver, particularly to the liver immunocompetent cells, and thereby improve the therapeutic efficacy by reducing interlobular collagen I deposition and MMP13 [ 86 ].…”

Section: Nanomedicine For Liver Fibrosis Therapymentioning

confidence: 99%

Recent Advances in Nanomedicine for the Diagnosis and Therapy of Liver Fibrosis

Bai

Zhai

2020

Nanomaterials

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Liver fibrosis, a reversible pathological process of inflammation and fiber deposition caused by chronic liver injury and can cause severe health complications, including liver failure, liver cirrhosis, and liver cancer. Traditional diagnostic methods and drug-based therapy have several limitations, such as lack of precision and inadequate therapeutic efficiency. As a medical application of nanotechnology, nanomedicine exhibits great potential for liver fibrosis diagnosis and therapy. Nanomedicine enhances imaging contrast and improves tissue penetration and cellular internalization; it simultaneously achieves targeted drug delivery, combined therapy, as well as diagnosis and therapy (i.e., theranostics). In this review, recent designs and development efforts of nanomedicine systems for the diagnosis, therapy, and theranostics of liver fibrosis are introduced. Relative to traditional methods, these nanomedicine systems generally demonstrate significant improvement in liver fibrosis treatment. Perspectives and challenges related to these nanomedicine systems translated from laboratory to clinical use are also discussed.

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Dexamethasone Conjugation to Biodegradable Avidin-Nucleic-Acid-Nano-Assemblies Promotes Selective Liver Targeting and Improves Therapeutic Efficacy in an Autoimmune Hepatitis Murine Model

Cited by 42 publications

References 43 publications

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Super Resolution Microscopy of SUMO Proteins in Neurons

Recent Advances in Nanomedicine for the Diagnosis and Therapy of Liver Fibrosis

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