Harnessing Nanomedicine to Combat Hepatic Fibrosis

Published

11 months ago

December 21, 2023

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By Dr. Sanchari Sinha Dutta, Ph.D. Reviewed by Danielle Ellis, B.Sc.

Understanding nanomedicines
Nanomedicine in hepatic fibrosis diagnosis
Nanomedicine in hepatic fibrosis treatment
Nanomedicine in drug delivery
Nanomedicine in targeted drug delivery
Future perspectives
References
Further reading

Hepatic fibrosis is an abnormal wound-healing response triggered by chronic liver diseases, including non-alcoholic fatty liver disease, viral or alcoholic hepatitis, and Wilson’s disease. The response is characterized by excessive synthesis and deposition of extracellular matrix (ECM) components, which can further trigger the development of liver cirrhosis, liver failure, or liver cancer.

Image Credit: Shidlovski/Shutterstock.com

Hepatic stellate cells (HSCs) account for 13% of total liver cells. These cells are activated and transformed into myofibroblasts in response to liver injury. Activation of these cells is a major hallmark of hepatic fibrosis.

Many therapeutic approaches are emerging to inhibit the development of hepatic fibrosis. These approaches include anti-inflammatory and hepato-protective strategies, inhibition of hepatic stellate cell (HSC) activation and proliferation, inhibition of ECM synthesis and induction of ECM degradation, and gene therapy.

Despite promising outcomes in preclinical trials, most of the anti-hepatic fibrosis drugs fail to show desired efficacy in human clinical trials. The complex and multifactorial pathophysiology of hepatic fibrosis is the main reason behind treatment failure. Moreover, higher dosage of these drugs is associated with many health adversities. This highlights the need to develop novel therapeutic interventions for hepatic fibrosis. Understanding nanomedicines

Nanomedicine refers to the application of nanoparticles in the diagnosis and treatment of diseases. Various nanotechnology-based methods have been developed to design, modify, and apply small-diameter nanoparticles (10-500 nanometers) for therapeutic purposes.

Nanomedicines have a high potential for targeted drug delivery. Nanoparticles can be used to develop cell- or tissue-specific devices that enable precise delivery of drugs at the disease site. Moreover, physicochemical characteristics of nano-drug carriers, such as size, shape, and surface properties, can be modified to enable targeted drug delivery. Nanomedicine in hepatic fibrosis diagnosis

Nanomedicine has shown promising outcomes in the diagnosis and treatment of hepatic fibrosis. Ultrasound imaging and blood testing are standard approaches for hepatic fibrosis diagnosis. However, these methods lack diagnostic accuracy. Moreover, invasive biopsy-based diagnosis of hepatic fibrosis is associated with tissue damage.

The use of magnetic nanoparticles in magnetic resonance imaging (MRI) has shown promising outcomes in hepatic fibrosis diagnosis. Dextran-stabilized superparamagnetic iron oxide nanoparticles and citrate-coated ultrasmall iron oxide nanoparticles are used as MRI contrast agents to diagnose hepatic fibrosis accurately.

Image Credit: VesnaArt/Shutterstock.com Related StoriesImmunoregulatory nanomedicines for the prevention and treatment of respiratory diseasesEffects of nanoparticles on gouty arthritis in animal models of goutExploring biodistribution of cannabidiol nanoparticles and nanoemulsion after intrathecal administration

Iron nanoparticles and indocyanine green are used as photographic developers in MRI and near-infrared imaging, respectively. For targeting HSCs and early detection of hepatic fibrosis, a construct has been formed by coating iron nanoparticles with silicon dioxide and then coupling it with arginine–glycine–aspartic acid. Near-infrared fluorescence and MRI have shown that the construct can precisely identify fibrotic regions in the liver.

A novel contrast agent for MRI has been developed using zero-valent iron-based nanoparticles. The contrast agent has been functionalized with liver polysaccharide pullulan and fluorescent carbon dots to obtain a dual imaging contrast agent, which has shown high efficacy in targeted liver imaging and optical imaging.

Besides MRI contrast agents, ultrasound agents combined with targeting peptides have been developed for early and non-invasive diagnosis of hepatic fibrosis. High-contrast images of fibrotic regions and adjacent tissues in the liver have been obtained by conducting ultrasound imaging using PLGA polymer-coated and cyclic RGD peptide-modified core–shell perfluorooctyl bromide. Nanomedicine in hepatic fibrosis treatment

Inorganic nanoparticles with distinct bioactive properties can be used as therapeutic agents for hepatic fibrosis. Titanium dioxide and silicon dioxide nanoparticles have been found to inhibit the expression and induce the degradation of collagen I. Moreover, they exhibit anti-adhesive and anti-migratory effects, which collectively make them suitable agents to treat hepatic fibrosis.

In animals, manganese oxide nanoparticles with antioxidant properties and cerium oxide nanoparticles with anti-inflammatory properties have been found to reduce liver steatosis, portal hypertension, and liver fibrosis. Similarly, gold nanoparticles have been found to inhibit HSC activation and prevent hepatic fibrosis in animals. Nanomedicine in drug delivery

Nanoparticles are widely used as drug carriers for treating hepatic fibrosis. The most efficient drug carriers are lipid-based nanoparticles because of their good biocompatibility and low toxicity.

Studies using mouse hepatic fibrosis models have shown that cationic lipid nanoparticles loaded with procollagen gene-targeting siRNA can be retained in the liver to specifically inhibit procollagen expression and prevent hepatic fibrosis progression without side effects.

PLGA and eudragit nanoparticles have been used to deliver phyllanthin and silymarin, respectively, to reduce liver damage markers, inhibit inflammation, and prevent hepatic fibrosis.

High biocompatibility and low immunogenicity make protein-based nanoparticles a promising drug carrier for treating hepatic fibrosis. Curcumin-loaded zein nanospheres have shown high potency in reducing expressions of collagen I and matrix metalloproteinases (MMPs) in fibrotic liver.

Human serum albumin has been used to deliver dexamethasone nanoparticles to non-parenchymal hepatic cells, which play crucial roles in hepatic fibrosis pathogenesis. Similarly, glucose-modified albumin nanoparticles loaded with berberine have been found to inhibit HSC proliferation more efficiently and prevent hepatic fibrosis than berberine alone. Nanomedicine in targeted drug delivery

Different nano-formulations have been designed for targeted drug delivery in hepatic fibrosis. For targeted inhibition of HSCs and prevention of hepatic fibrosis, liposome-based formulations loaded with anti-fibrotic drugs and HSC-targeting components have been developed. Similarly, polymer-based nanoparticles coupled with vitamin A have been developed to target HSCs specifically.

Cyclic peptide-modified liposomes and CXCR4 antagonist AMD3100-conjugated liposomes have been developed to target HSCs. Besides HSCs, various nano-formulations have been designed to target hepatic macrophages, which play vital roles in hepatic fibrosis pathogenesis. Future perspectives

Strategies that can be adopted to increase the clinical application of nanomedicine in hepatic fibrosis include the development of highly sensitive nanomedicine systems that can respond to endogenous and exogenous stimuli and release payload at target sites.

Long-term toxicity, immunogenicity, and pharmacokinetics of nanomedicine systems should also be investigated systematically. References Bai X., et al. 2020. Recent Advances in Nanomedicine for the Diagnosis and Therapy of Liver Fibrosis. Nanomaterials. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599596/ Tan Z., et al. 2021. Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy. Frontiers in Cell and Developmental Biology. https://www.frontiersin.org/articles/10.3389/fcell.2021.730176/full Singh S., et al. 2023. Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics. Molecules. https://www.mdpi.com/1420-3049/28/6/2811

Further ReadingAll Nanomedicine ContentApplications of NanomicellesInhaled Nanomedicines and Pulmonary DiseaseNanodelivery Drug SystemsNanoencapsulation in PharmaceuticalsMore…

Last Updated: Dec 13, 2023

Business

Energy bills to rise again from January but spring falls to come, research firm Cornwall Insight forecasts

Published

3 hours ago

November 18, 2024

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Energy bills to rise again from January but spring falls to come, research firm Cornwall Insight forecasts

Energy bills are to rise again next year, according to a respected forecaster.

Costs from January to March are projected to rise another 1% to £1,736 a year for the average user, according to research firm Cornwall Insight.

The energy price cap, which sets a limit on how much companies can charge per unit of electricity, is also expected to rise, costing typical households an extra £19 a year.

It’s a further increase after energy costs rose 10% from October.

After the latest hike, there were hopes of a fall in the new year, but volatile wholesale gas and electricity markets are still above historic average costs.

Money blog: Supermarket-own champagne beats expensive brands in taste test

Prices have gone up due to supply concerns arising from Russia‘s war in Ukraine, and maintenance of Norwegian gas infrastructure.

But spring is expected to herald a reduction as is October 2025, Cornwall Insight said.

Every three months energy regulator Ofgem revises the cap based on wholesale costs.

The official January price cap announcement will be made on Friday.

It comes as millions of pensioners lost their automatic winter fuel allowance payment after the government means-tested the benefit.

Meanwhile, Cornwall Insight’s principal consultant Dr Craig Lowrey warned “millions” of households won’t heat their homes to “recommended temperatures, risking serious health consequences” with bills on the rise.

“With it being widely accepted that high prices are here to stay, we need to see action,” he said, suggesting options like cheaper rates for low-income homes, benefit restructuring, or other targeted support for the vulnerable “must be seriously considered”.

The energy price cap system is being reviewed by Ofgem with possible changes to the standing charge coming over the next year.

The long-lasting solution to high energy bills is the transition to UK-produced renewable power, the firm said.

“While there will be upfront costs, this shift is essential to building a sustainable and secure energy system for the future.”

UK

Masked burglars ‘raid’ Windsor Castle grounds ‘while William, Kate and children slept at home on estate’

Published

3 hours ago

November 18, 2024

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Masked burglars 'raid' Windsor Castle grounds 'while William, Kate and children slept at home on estate'

Masked burglars have stolen farm vehicles from the Windsor Castle estate while members of the Royal Family are believed to have been asleep nearby.

Two men scaled a 6ft fence on the night of 13 October and used a stolen truck to break through a security gate, The Sun first reported.

The pair then fled with a pick-up and a quad bike that were stored in a barn.

The King and Queen were not in residence.

But the Prince and Princess of Wales, along with their three children George, 11, Charlotte, nine, and six-year-old Louis were believed to have been in their home, Adelaide Cottage, on the estate, according to The Sun.

The family moved there in 2022.

In a statement, Thames Valley Police said: “At around 11.45pm on Sunday 13 October, we received a report of burglary at a property on Crown Estate land near to the A308 in Windsor.

“Offenders entered a farm building and made off with a black Isuzu pick-up and a red quad bike. They then made off towards the Old Windsor/Datchet area.

“No arrests have been made at this stage and an investigation is ongoing.”

On Christmas Day 2021, a man climbed a fence at Windsor Castle armed with a crossbow and claimed he wanted to kill Queen Elizabeth II.

Jaswant Singh Chail was handed a nine-year custodial sentence for treason, possession of an offensive weapon and making threats to kill.

UK

UK told to expect ‘disruptive snow’ as warnings cover large parts of country

Published

3 hours ago

November 18, 2024

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UK told to expect 'disruptive snow' as warnings cover large parts of country

The UK is braced for “disruptive snow” as yellow weather warnings cover large parts of the country until Tuesday – with the Met Office saying there is the “potential” for the alerts to be “escalated”.

The forecaster has warned up to 20cm of snow may accumulate in the worst affected areas as the country experiences its “first taste of winter”.

The Met Office has also told people to expect ice, cold temperatures and wintry showers this week.

Check the forecast in your area

A yellow warning for snow and ice is in place for much of the north of the country – covering areas in the East Midlands, Yorkshire, Wales and the north of England – from 7pm on Monday night to 10am on Tuesday morning.

Those in the impacted areas have been told power cuts are possible and mobile phone coverage might be affected.

The Met Office has said there is a “slight chance” some rural communities could be cut off and that bus and train services may be delayed or cancelled.

People are also warned to be careful not to slip or fall on icy surfaces.

The Met Office has said there will be bright spells across northern and eastern areas throughout today, but rain in the south and west will gradually spread northeastwards and turn to snow over northern hills.

Tom Morgan, Met Office meteorologist, said: “We could see some disruptive snow in the Pennine regions, in particular, the Peak District as well, especially Monday night, but we could well see some impacts lasting on until Tuesday morning’s rush hour.

“Even down to lower levels, we could well see some snow as well, so quite a bit of disruption possible by Tuesday morning, and then the week ahead is likely to stay cold nationwide, a windy day on Tuesday, and then winter showers through the week ahead.”

Mr Morgan said that despite a “mild” start to the month, the cold conditions are more typical of “mid-winter to late-winter”.

“What we can say is that it’s going to be very cold for the time of year, there will be widespread overnight frosts, and a few locations where there’s snow on the ground,” he continued.

Meanwhile, a yellow snow and ice weather warning that came into force at 4pm on Sunday will end at 11am this morning.

The warning covers the northern tip of Scotland and people there have been told there may be icy patches on some untreated roads, pavements and cycle paths.

The Met Office has said there is “potential” for both yellow warnings to be “escalated”.

In southern England, a typical maximum temperature for this time of year is 11C (52F), but daytime highs for the week ahead are forecast to be around 5C (41F), while some parts of Scotland will reach “only just above freezing”, Mr Morgan said.

The meteorologist said the public can best prepare for the wintry weather by checking their cars are suitable for icy and potentially snowy conditions and to take extra supplies including food, blankets and a fully charged mobile phone with them on journeys.

He added there were “likely” to be changes to the weather warnings in the coming days, and that “winter flurries” could be seen in the south of England later in the week.

Despite the cold conditions, the “whole of the UK” will enjoy more sunshine this week, the meteorologist added.

He said: “There’ll be some snow showers in the peripheries of the UK, particularly northern Scotland, and down the east and the west coast, but if you live inland and you live in the south, there’ll be lots of sparkly blue skies on the most days through Tuesday to Friday.”

It comes as a cold weather alert issued by the UK Health Security Agency, which was introduced at 9am on Sunday, will be in place until 9am on Thursday.

It covers a large area of England, north of Northhampton. The alert is triggered when there is a risk that healthcare services might face extra pressure and is designed to prepare those who are “particularly vulnerable” and “likely to struggle to cope”.