NT/ Lung-targeting lipid nanoparticles with CRISPR components successfully treat cystic fibrosis mouse models

Paradigm

Published in

Paradigm

11 min readJul 2, 2024

Nanotechnology & nanomaterials biweekly vol.58, 25th June — 2nd July

TL;DR

A team of medical researchers from the University of Texas Southwestern Medical Center, Case Western Reserve University School of Medicine and ReCode Therapeutics has developed a way to send gene-editing tools to the lungs to repair the faulty gene associated with cystic fibrosis.
Researchers at the National Graphene Institute have made a discovery that could revolutionize energy harnessing and information computing. Their study, published in Nature, reveals how electric field effects can selectively accelerate coupled electrochemical processes in graphene.
A research team from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has developed an environmentally friendly way to deliver pesticides using porous microspheres made of halloysite nanotubes (HNTs).
An international research team used a common amino acid, tyrosine, packaged as a nanomedicine, to change the metabolism of melanoma, a deadly skin cancer, and prevent cancer growth.
Researchers at Nelson Mandela University, Gzeberha, South Africa, have discovered a new type of powder for dusting fingerprints. It allowed them to image their nanoscale details more clearly while deepening the contrast between ridges and valleys.

Nanotech Market

Nanotechnology deals with the ability to see, understand, measure, predict, produce or control matter at the nanoscale (below 100 nanometers). The realm of nanotechnology lies between 0.1 and 100 nanometers, wherein a nanometer is defined as one-thousandth of a micron. As a versatile technology with widespread applications in a wide range of end-use sectors, nanotechnology is currently facing a mixed bag of challenges and opportunities as the COVID-19 pandemic continues to spread across the globe. With the world fighting its biggest public health crisis in history, nanotechnology healthcare applications are storming into the spotlight led by the focus on nano intervention in terms of designing effective ways to identify, diagnose, treat and eliminate the spread of COVID-19 infections. Their role as nanocarriers has the potential to design risk-free and effective immunization strategies. In the post-COVID-19 period, the use of nanotechnology solutions in the production of a multitude of devices & products will continue to grow.

Amid the COVID-19 crisis, the global market for Nanotechnology estimated at US$42.2 Billion in the year 2020, is projected to reach a revised size of US$70.7 Billion by 2026, growing at a CAGR of 9.2% over the analysis period. Nanocomposites, one of the segments analyzed in the report, is projected to record an 8.7% CAGR and reach US$35.4 Billion by the end of the analysis period. After a thorough analysis of the business implications of the pandemic and its induced economic crisis, growth in the Nanomaterials segment is readjusted to a revised 10.1% CAGR for the next 7-year period.

Global nanotechnology market to reach US $126.8 billion by the year 2027. Amid the COVID-19 crisis, the global market for Nanotechnology is estimated at US $54.2 billion in the year 2020 and is projected to reach a revised size of US $126 billion.

Latest News & Research

In vivo editing of lung stem cells for durable gene correction in mice

by Yehui Sun et al in Science

A team of medical researchers from the University of Texas Southwestern Medical Center, Case Western Reserve University School of Medicine and ReCode Therapeutics has developed a way to send gene-editing tools to the lungs to repair the faulty gene associated with cystic fibrosis.

In their study, published in the journal Science, the group overcame problems that have hampered previous therapies, and believe that their method will soon be used to treat human patients.

Mattijs Bulcaen and Marianne Carlon with KU Leuven, in Belgium, have published a Perspective piece in the same journal issue outlining the work by the team on this new effort.

Cystic fibrosis is a genetic disease that impacts the lungs and GI tract — a faulty gene results in a sticky mucous buildup in the lungs and throughout the digestive system. Many therapies have been developed to treat symptoms of the disease, but there is still no cure.

In the recent past, researchers have attempted to send gene-editing tools into the lungs to repair the faulty gene, but thus far, such efforts have failed due to the difficulty in getting them past both the immune system and the mucus.

Other efforts have involved sending therapies to the lungs through the bloodstream. They also failed due to the liver filtering them out before they could reach the lungs.

In this new study, the researchers developed a therapy based on this latter approach, but have found a way to prevent it from getting stuck in the liver.

The research team tweaked the gene editing machinery to prevent the lipid nanoparticles from being trapped in the liver. They also tweaked them to target the basolateral side of the lung epithelial lining once they arrived through the bloodstream. This allowed the nanoparticles to find their way to several types of lung cells, including basal cells.

The researchers tested the approach in mice genetically engineered to have human-like cystic fibrosis. The therapy proved to be highly effective — the researchers found the gene editor had made its way to the desired targets and fixed the mutation in half of the mice being tested.

In monitoring the successfully treated mice, the research team found that it relieved symptoms for up to 22 months.

Control of proton transport and hydrogenation in double-gated graphene

by Jincheng Tong et al in Nature

Researchers at the National Graphene Institute have made a discovery that could revolutionize energy harnessing and information computing. Their study, published in Nature, reveals how electric field effects can selectively accelerate coupled electrochemical processes in graphene.

Electrochemical processes are essential in renewable energy technologies like batteries, fuel cells, and electrolyzers. However, their efficiency is often hindered by slow reactions and unwanted side effects. Traditional approaches have focused on new materials, yet significant challenges remain.

The Manchester team, led by Dr. Marcelo Lozada-Hidalgo, has taken a novel approach. They have successfully decoupled the inseparable link between charge and electric field within graphene electrodes, enabling unprecedented control over electrochemical processes in this material. The breakthrough challenges previous assumptions and opens new avenues for energy technologies.

Dr. Lozada-Hidalgo sees this discovery as transformative and said, “We’ve managed to open up a previously inaccessible parameter space. A way to visualize this is to imagine a field in the countryside with hills and valleys. Classically, for a given system and a given catalyst, an electrochemical process would run through a set path through this field.
“If the path goes through a high hill or a deep valley — bad luck. Our work shows that, at least for the processes we investigated here, we have access to the whole field. If there is a hill or valley we do not want to go to, we can avoid it.”

The study focuses on proton-related processes fundamental for hydrogen catalysts and electronic devices. Specifically, the team examined two proton processes in graphene:

Proton transmission: This process is important for developing new hydrogen catalysts and fuel cell membranes.
Proton adsorption (Hydrogenation): Important for electronic devices like transistors, this process switches graphene’s conductivity on and off.

Traditionally, these processes were coupled in graphene devices, making it challenging to control one without impacting the other. The researchers managed to decouple these processes, finding that electric field effects could significantly accelerate proton transmission while independently driving hydrogenation. This selective acceleration was unexpected and presents a new method to drive electrochemical processes.

Highlighting the broader implications in energy applications, Dr. Jincheng Tong, first author of the paper, said, “We demonstrate that electric field effects can disentangle and accelerate electrochemical processes in 2D crystals. This could be combined with state-of-the-art catalysts to efficiently drive complex processes like CO2 reduction, which remain enormous societal challenges.”
Dr. Yangming Fu, co-first author, pointed to potential applications in computing and said, “Control of these processes gives our graphene devices dual functionality as both memory and logic gate. This paves the way for new computing networks that operate with protons. This could enable compact, low-energy analog computing devices.”

Spherical Assembly of Halloysite Clay Nanotubes as a General Reservoir of Hydrophobic Pesticides for pH‐Responsive Management of Pests and Weeds

by Guopeng Teng et al in Small

A research team led by Prof. Wu Zhengyan and Zhang Jia from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences has developed a new environmentally friendly way to deliver pesticides using porous microspheres made of halloysite nanotubes (HNTs).

These microspheres are formed by reversible metal-ligand coordination interactions, making them responsive to changes in pH, humidity, and enzymes. The results were published in the journal Small.

Traditional pesticide formulations are limited by their rapid release, resulting in low efficacy and serious environmental risks. To address this, researchers are developing greener pesticides with controlled-release properties. Improving the release of existing active ingredients is a simpler and more effective way to improve efficacy and reduce ecological risks, thereby reducing misuse.

In this study, the researchers loaded the insecticide avermectin (AVM) and the herbicide prometryn (PMT) into the HNT microspheres. They then coated the microspheres with a tannic acid/iron complex, fabricating two controlled-release pesticides called HCEAT and HCEPT. These new formulations have high pesticide loading capacities and effectively release the pesticides in response to weak acids.

In addition, these pesticides show improved ultraviolet light resistance, better foliar adhesion, and reduced leaching to soil, with no observed adverse effects on plants and soil organisms.

“This approach could lead to more efficient and environmentally friendly pesticide use in agriculture, supporting sustainable farming practices,” said Teng Guopeng, first author of the study.

Nutrient-delivery and metabolism reactivation therapy for melanoma

by Yang Chen et al in Nature Nanotechnology

An international research team used a common amino acid, tyrosine, packaged as a nanomedicine, to change the metabolism of melanoma, a deadly skin cancer, and prevent cancer growth.

Australia has the highest rate of skin cancer in the world. This new approach could be combined with current therapies to better treat melanoma. The technique also has the potential to treat other types of cancer.

The study, “Nutrient-delivery and metabolism reactivation therapy for melanoma”, was led by Professor Wenbo Bu from Fudan University and Professor Dayong Jin from the University of Technology Sydney, and has been published in Nature Nanotechnology.

Tyrosine has limited bioavailability in living organisms. However, the researchers used a new nanotechnology technique to package it into tiny particles called nanomicelles, which are attracted to cancer cell membranes, and break down easily, boosting absorption.

The research team then tested the innovative treatment in mice and in human-derived melanoma cells in the lab and found that the tyrosine nanomicelles reactivated dormant metabolic pathways, triggered melanin synthesis, and inhibited tumor growth.

“Uncontrolled rapid growth is a key feature that distinguishes cancer cells from normal cells. In cancer cells some metabolic pathways are over-activated, and others are suppressed, to create the environment necessary for rapid spread,” said Professor Jin.
“While a few metabolism-based drugs for cancer have been developed previously, such as aromatase inhibitors impeding estrogen synthesis in breast cancer and HK2 inhibitors targeting glycolysis in various cancers, these work by suppressing over-activated metabolic pathways,” he said.
“Our research shows for the first time that cancer can be stopped by reactivating metabolic pathways that are dormant. And this can be done using simple nutrients, such as amino acids, sugars, and vitamins, which are safe, readily available and well tolerated,” said Professor Bu.

Different types of cancer will respond to different nutrients. Melanoma cells develop from melanocytes — skin cells that produce melanin. Tyrosine is needed to produce melanin and it can stimulate melanin production, hence its effectiveness with melanoma.

The reactivation of melanin synthesis forces the melanoma cell to reduce glycolysis, the process of converting sugar to energy, which is believed to be the mechanism for its anti-cancer effect.

Melanoma cells are also susceptible to heat stress. The researchers found that by combining tyrosine nanomicelle treatment with near-infrared laser treatment, they were able to eradicate melanoma in mice after six days and it did not reoccur during the study period.

The findings suggest a promising new frontier in the use of nanomedicine for cancer therapy.

Nanoarchitectonics of WLC-H3PO4–MnFe2O3 nanocomposite for latent fingerprint detection

by B.G. Fouda-Mbanga et al Hybrid Advances

Researchers led by Bienvenu Gael Fouda-Mbanga at Nelson Mandela University, Gzeberha, South Africa, have discovered a new type of powder for dusting fingerprints. It allowed them to image their nanoscale details more clearly while deepening the contrast between ridges and valleys. This work is now published in Hybrid Advances.

Fingerprint detection is one of the most important techniques in forensic investigation. When fingerprints are dusted with a carbon-based powder, the material will adhere to the moisture and grease left behind by the unique patterns of ridges and valleys on the perpetrator’s fingertip. The resulting pattern can then be analyzed under a microscope, and compared with suspects’ fingerprints.

Made from manganese-doped iron oxide nanoparticles and coated in an activated wool char, this new material could help forensic investigators solve crimes more easily.

Recently, metal-oxide nanoparticles have become increasingly popular in fingerprint detection. Not only are they easy to produce, but they also have a high surface area and chemical reactivity, allowing them to interact strongly with the chemical compounds contained in fingerprint residues.

When coated in carbon, these nanoparticles create a deeper contrast in fingerprint images, making them far easier to analyze.

In their study, Fouda-Mbanga’s team fabricated their iron oxide nanoparticles using a low-cost, environmentally friendly “hydrothermal” method. They then coated the particles with activated charred wool. This widely available agricultural waste product is chemically inert, making it safer to use than conventional carbon-based powders, while also enhancing the stability of the more reactive nanoparticles.

To examine their powder’s performance, the researchers used it to dust fingerprint residues on a non-porous aluminum surface. They then employed several different types of electron microscopy and light spectroscopy to image them.

The images they produced were incredibly promising, revealing details down to a nanoscale resolution while showing a starker contrast than many types of powder tested in previous studies. Following this success, Fouda-Mbanga’s team now hopes that their approach to nanoparticle fabrication could soon be applied more widely in forensic investigation.