Researchers break diffraction barrier in super-resolution microscopy

Good news! This could be a breakthrough!

"... have developed a groundbreaking super-resolution imaging technology that allows scientists to visualize molecular structures with sub-angstrom-level localization precision — three orders of magnitude beyond the nanometer limits of standard fluorescent dyes — while drastically simplifying the imaging process.

Unlike traditional dyes that fade rapidly under illumination and limit data collection, the platform, called U-STORM (Upconversion enabled Stochastic Optical Reconstruction Microscopy) utilizes a new class of compositionally engineered upconverting nanoparticles (UCNPs) that blink spontaneously and indefinitely. ..."

From the abstract:

"Single-molecule localization microscopy enables high-resolution biological imaging, but its precision is limited by the rapid photobleaching of conventional fluorophores.

Multicolour imaging is further constrained by the need for spectrally distinct dyes requiring separate excitations or sequential acquisition.

Here we show that small (~10 nm) upconverting nanoparticles can be compositionally tuned to exhibit spontaneous, sustained blinking under single near-infrared excitation without optical or chemical modulation.

By adjusting sensitizer (Yb3+)–emitter (Tm3+/Er3+) ratios, we identify a regime with intrinsic ON–OFF switching and low duty cycles (~0.9%) without photobleaching or statistical aging, enabling repeated localizations and sub-ångström precision (0.62 Å over 88,000 localizations) in upconversion-enabled stochastic optical reconstruction microscopy.

By elucidating the underlying physical mechanism of this blinking, we engineered blue- and red-emitting probes for multicolour upconversion-enabled stochastic optical reconstruction microscopy.

This technique enables the resolution of tightly packed UCNPs and the visualization of epidermal growth factor receptor dimers and multimers on cell membranes at single-protein resolution, all achieved with a simple optical setup without imaging buffers."

MIT and Broad Institute researchers break diffraction barrier in super-resolution microscopy | MIT News | Massachusetts Institute of Technology "New U-STORM imaging technology lets scientists view molecular structures in subatomic detail — about 1,000 times clearer than traditional dyes — while making the microscope process much simpler."

Spontaneous and indefinite blinking in upconverting nanoparticles for ångström-precision multicolour super-resolution imaging (open access)

Fig. 1: U-STORM workflow and route to ångström-level precision.

Fig. 3: Super-resolution imaging with high precision and accuracy using blue-emitting U-STORM probe.

Single-molecule tracker illuminates workings of cancer-related proteins

Good news! Cancer is history (soon)!

"Using a powerful single-molecule imaging method they developed, a research team ... unveiled a dynamic view of how some cancer-related proteins interact in living cells.

The technique relies on highly stable nanoparticle probes that brightly illuminate individual molecules for long periods of time. The researchers used their method to observe, for the first time, individual receptors as they move around the cell membrane, attaching to and then letting go of other receptors to alter signaling within the cell. ..."

From the highlights and abstract:

"Highlights

• Multicolor UCNPs enable specific ErbB labeling for long-term tracking (UCNP-SPT)

• Bayesian diffusion analysis and dimer lifetimes quantify ErbB receptor mutant dynamics

• UCNP-SPT shows HER2/HER3 homodimerization and how mutations affect dimer stability

• UCNP-SPT reveals EGFR/HER2/HER3 heterodimers and ligand effects on dimer stability

Summary

Dimerization is crucial for the activation of ErbB family receptors, yet the real-time dynamics and effects of oncogenic mutations remain unclear.

Here, we performed long-term, multicolor single-particle tracking (SPT) of EGFR, HER2, and HER3 in living cells using upconverting nanoparticles (UCNPs), which do not photobleach.

Our technique enables continuous observation of receptor interactions, revealing details of their dimerization dynamics.

Oncogenic EGFR mutations promote stable, ligand-independent dimerization. Unexpectedly, both HER2 and HER3 exhibit constitutive homodimerization, prompting a revised model for their activation mechanisms.

HER2 mutations modestly enhance homodimer stability compared with EGFR mutations, while HER3 mutations destabilize homodimers, suggesting that HER3 homodimerization sequesters HER3 and limits heterodimerization with other receptors.

We also identified stable, ligand-independent heterodimers among all three receptors, further stabilized by ligand stimulation. These insights offer a comprehensive ErbB interaction network, elucidating diverse dimerization mechanisms and implications for oncogenic signaling."

Single-molecule tracker illuminates workings of cancer-related proteins | MIT News | Massachusetts Institute of Technology "Researchers can now use custom-built microscopy and nanotechnology to tag and follow the activity of individual proteins in real-time."

ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging

Graphical abstract

A new approach to cancer vaccination yields more powerful T cells

Good news! Cancer is history (soon)!

"... have developed a new way to amplify the T-cell response to mRNA vaccines — an advance that could lead to much more powerful cancer vaccines and stronger protection against infectious diseases.

Most vaccines generate both antibodies and T cells that can target the vaccine antigen by activating antigen-presenting cells, such as dendritic cells.

In this study, the researchers boosted the T-cell response with a new type of vaccine adjuvant (a material that can help stimulate the immune system). The new adjuvant consists of mRNA molecules encoding genes that turn on immune signaling pathways and promote a supercharged T-cell response. 

In studies in mice, this mRNA-encoded adjuvant enabled the immune system to completely eradicate most tumors, either on its own or delivered along with a tumor antigen. The adjuvant also boosted the T-cell response to vaccines against influenza and Covid-19. ...

As an alternative approach, the researchers decided to deliver mRNA strands encoding two genes, IRF8 and NIK, which are involved in antigen presentation and can switch immune cells into a more active state. ...

The researchers tested the immune-remodeling mRNAs in several mouse models of cancer, including an aggressive bladder cancer, colon carcinoma, melanoma, and metastatic lung cancer.

In nearly all of these mice, the injected mRNA stimulated a strong T-cell response that significantly slowed tumor growth and in many cases completely eradicated the tumors. This happened even when the mice were not given a vaccine against a specific cancer antigen. When they were, the response was even stronger. ..."

From the abstract:

"Although immunotherapy has benefited a subset of persons with cancer, its broader efficacy remains limited, primarily because of an immunosuppressive tumor microenvironment characterized by insufficient numbers of functional tumor-specific T cells, antigen-presenting cells (APCs) and tumor-infiltrating lymphocytes.

Here we engineer immune cells in the tumor microenvironment using lipid nanoparticles (LNPs) to deliver immune-remodeling mRNAs (IR-mRNAs) encoding NF-κB-inducing kinase or interferon regulatory factor 8. These IR-mRNAs activate APCs in tumors, significantly increasing activated type 1 conventional dendritic cells, immunostimulatory cytokines and priming antitumor CD8+ T cells.

IR-mRNAs encapsulated in LNPs elicited durable antitumor responses in multiple syngeneic mouse tumor models through both intratumoral and intravenous delivery.

Coadministration of IR-mRNA and ovalbumin mRNA elicited a ~10-fold increase in antigen-specific CD8+ T cell responses, sustained long-term memory and effectively prevented tumor growth in vaccinated mice.

Additionally, coadministration of IR-mRNA and hemagglutinin mRNA enhanced the humoral response ~5-fold and the cellular response ~15-fold, underscoring their potential as adjuvants for boosting adaptive immunity."

A new approach to cancer vaccination yields more powerful T cells | MIT News | Massachusetts Institute of Technology "Using immune-remodeling mRNA molecules, researchers generated T cells that can slow tumor growth and, in some cases, eradicate tumors."

Immune-remodeling mRNAs expressing IRF8 or NIK generate durable antitumor immunity in multiple cancer models (no public access)

AI-generated sensors open new paths for early cancer detection

Good news! Detecting cancer the earlier, the better! Cancer is history (soon)!

Apparently, the featured research article does not really describe new early cancer detection. Or in other words, there is a mismatch!

"... The researchers developed an AI model to design peptides (short proteins) that are targeted by enzymes called proteases, which are overactive in cancer cells. Nanoparticles coated with these peptides can act as sensors that give off a signal if cancer-linked proteases are present anywhere in the body.

Depending on which proteases are detected, doctors would be able to diagnose the particular type of cancer that is present. These signals could be detected using a simple urine test that could even be done at home. ...

More than a decade ago, Bhatia’s lab came up with the idea of using protease activity as a marker of early cancer. The human genome encodes about 600 proteases, which are enzymes that can cut through other proteins, including structural proteins such as collagen. They are often overactive in cancer cells, as they help the cells escape their original locations by cutting through proteins of the extracellular matrix, which normally holds cells in place.

The researchers’ idea was to coat nanoparticles with peptides that can be cleaved by a specific protease. These particles could then be ingested or inhaled. As they traveled through the body, if they encountered any cancer-linked proteases, the peptides on the particles would be cleaved.

Those peptides would be secreted in the urine, where they could be detected using a paper strip similar to a pregnancy test strip. Measuring those signals would reveal the overactivity of proteases deep within the body. ...

The researchers have used this approach to demonstrate diagnostic sensors for lung, ovarian, and colon cancers. ..."

From the abstract:

"Proteases, enzymes that play critical roles in health and disease, exert their function through the cleavage of peptide bonds. Identifying substrates that are efficiently and selectively cleaved by target proteases is essential for studying protease activity and for harnessing it in protease-activated diagnostics and therapeutics.

However, the vast design space of possible substrates (c.a. 2010 amino acid combinations for a 10-mer peptide) and the limited accessibility of high-throughput activity profiling tools hinder the speed and success of substrate design.

We present CleaveNet, an end-to-end AI pipeline for the design of protease substrates. Applied to matrix metalloproteinases, CleaveNet enhances the scale, tunability, and efficiency of substrate design. CleaveNet generates peptide substrates that exhibit sound biophysical properties and capture not only well-established but also previously-uncharacterized cleavage motifs.

To control substrate design, CleaveNet incorporates a conditioning tag that steers peptide generation towards desired cleavage profiles, enabling targeted design of efficient and selective substrates. CleaveNet-generated substrates were validated experimentally through a large-scale in vitro screen, even in the challenging case of designing highly selective substrates for MMP13. We envision that CleaveNet will accelerate our ability to study and capitalize on protease activity, paving the way for in silico design tools across enzyme classes."

AI-generated sensors open new paths for early cancer detection | MIT News | Massachusetts Institute of Technology "Nanoparticles coated with molecular sensors could be used to develop at-home tests for many types of cancer."

Deep learning guided design of protease substrates (open access)

Fig. 1: A deep learning approach for protease substrate design.

Solar hydrogen can now be produced efficiently without the scarce metal platinum

Good news! This could be a breakthrough! Photocatalysis without platinum  instead of electrolysis!

However, what are the effects of hydrogen power at large scale on the environment?

I have previously blogged here oft my critical opinion about hydrogen and water! And always remember the Hindenburg disaster of 1937!

"A research team led by Chalmers University of Technology, Sweden, have presented a new way to produce hydrogen gas without the scarce and expensive metal platinum. Using sunlight, water and tiny particles of electrically conductive plastic, the researchers show how the hydrogen can be produced efficiently, sustainably and at low cost. ...

In a new study, published in the scientific journal Advanced Materials, a research team led by Professor Ergang Wang at Chalmers, show how solar energy can be used to produce hydrogen gas efficiently – and completely without platinum.  ...

The key to the new approach lies in advanced materials design of the electrically conductive plastic used in the process. This type of plastic, known as conjugated polymers, absorbs light efficiently, but is typically less compatible with water.

By adjusting the material properties at the molecular level, the researchers made the material much more water compatible.

“We also developed a way to form the plastic into nanoparticles that can enhance the interactions with water and boost the light-to-hydrogen process. The improvement comes from more loosely packed, more hydrophilic polymer chains inside the particles” ..."

From the abstract:

"While the interest in hydrogen photocatalysis from organic semiconductors is rapidly growing, there is a necessity to achieve hydrogen production without platinum (Pt), considering its price, availability and toxicity.

In this work, this is demonstrated that high hydrogen evolution reaction (HER) efficiencies can be achieved without the use of Pt. A series of low-cost conjugated polymers are designed around the dibenzothiophene-S,S-sulfoxide (BTSO) unit, and self-assembled as nanoparticles in water via the nanoprecipitation technique.

This is highlighted that how side chain engineering, nanoparticle morphology and pH influence the hydrogen evolution rate.

Optoelectronic properties are improved through a Donor-Acceptor structure, resulting in an unprecedented hydrogen evolution reaction rate of 209 mmol g−1 h−1 in the absence of Pt.

A clear correlation between high efficiencies and number of BTSO units within the polymer backbone can be established. The design rules pioneer the design of future organic materials is presented for a cost-efficient and sustainable hydrogen photocatalysis."

Solar hydrogen can now be produced efficiently without the scarce metal platinum | Chalmers

Highly Efficient Platinum-Free Photocatalytic Hydrogen Evolution From Low-cost Conjugated Polymer Nanoparticles (open access, published in July 2025)

Credits: Wasserstoff aus Sonnenlicht: Gelingt so der große Durchbruch?

In the reactor at the chemistry laboratory at Chalmers, bubbles of hydrogen gas can be easily seen with the naked eye as they form – showing that photocatalysis is happening efficiently.

Fig. 1 Reported Hydrogen Evolution Reaction (HER) rates in the literature, updated in January 2025, and compared to the HER rate achieved in this work.

Fig. 2 a) Chemical structure of the polymers synthesized through a Suzuki-Miyaura cross-coupling polycondensation, highlighting in blue the electron accepting BTSO unit and in pink the electron donating thiophene unit.

b) Schematic representation of the nanoprecipitation mechanism, resulting in water-dispersed nanoparticles.

c) Absorption,

d) nanoparticle size distribution and e) hydrogen evolution of PFBTSO and PFgBTSO nanoparticles dispersed in water. Absorption spectra intensities were normalised at 405 nm. Photocatalytic experiments were performed using 0.25 mg of polymer nanoparticles in 10 mL of water, 0.1 M of ascorbic acid, no additional Pt cocatalyst and under 1 sun.

Nanoparticle therapy reprograms tumor immune cells to attack cancer from within

Good news! Cancer is history (soon)!

"In their approach, when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR ... proteins on their own, and are converted into anticancer immune cells known as "CAR-macrophages." ...

CAR-macrophages, which have recently attracted attention as a next-generation immunotherapy, have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses ..."

From the abstract (emphasis added):

"Cancer immunotherapy employing chimeric antigen receptor (CAR) technology has achieved significant clinical success in hematologic malignancies, but faces limitations in solid tumors.

Among alternative strategies, CAR-macrophage therapy offers distinct advantages in solid tumor settings. However, current ex vivo approaches are hindered by inefficient gene transfer into macrophages and challenges in maintaining an antitumor macrophage phenotype.

Here, we report an in situ CAR-macrophage therapy via codelivery of mRNA and immunostimulant. By leveraging lipid nanoparticles (LNPs) designed to selectively transfect tumor-associated macrophages, we circumvent extensive ex vivo manipulation and achieve robust CAR expression directly within the tumor microenvironment.
Furthermore, codelivery of a stimulator of interferon genes (STING) agonist amplifies local immune activation, leading to reinforced CAR-macrophage functionality and enhanced antitumor effects in a mouse melanoma model. This in vivo strategy addressed key obstacles of CAR-macrophage therapy in solid tumors by enabling direct cellular targeting, potent immunomodulation, and simplified manufacturing.

Our findings suggest an LNP-enabled approach for CAR-macrophage immunotherapy to overcome the limitations associated with conventional CAR-T cell therapies."

Nanoparticle therapy reprograms tumor immune cells to attack cancer from within

In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant (no public access)

Schematic illustration

New nanoparticles stimulate the immune system to attack ovarian tumors

Good news! Cancer is history (soon)! This new therapy attacks metastatic tumors and has memory to prevent recurrence!

"... To elicit a better response, MIT researchers have designed new nanoparticles that can deliver an immune-stimulating molecule called IL-12 directly to ovarian tumors. When given along with immunotherapy drugs called checkpoint inhibitors, IL-12 helps the immune system launch an attack on cancer cells.

Studying a mouse model of ovarian cancer, the researchers showed that this combination treatment could eliminate metastatic tumors in more than 80 percent of the mice. When the mice were later injected with more cancer cells, to simulate tumor recurrence, their immune cells remembered the tumor proteins and cleared them again. ...

In the new study, the researchers modified the particles so that IL-12 would be released more gradually, over about a week. They achieved this by using a different chemical linker to attach IL-12 to the particles. ...

To make sure that the particles get to the right place, the researchers coat them with a layer of a polymer called poly-L-glutamate (PLE), which helps them directly target ovarian tumor cells. Once they reach the tumors, the particles bind to the cancer cell surfaces, where they gradually release their payload and activate nearby T cells. ..."

From the abstract:

"Immunotherapies such as immune checkpoint inhibitors are effective in treating several advanced cancers, but these treatments have had limited success in metastatic ovarian cancer.

Here we engineered liposomal nanoparticles carrying a poly-ʟ-arginine/poly-ʟ-glutamate coating that promotes their binding and retention on the surface of ovarian cancer cells. Covalent anchoring of the potent immunostimulatory cytokine interleukin-12 (IL-12) to phospholipid head groups of the liposome core enabled the polymer-coated particles to concentrate IL-12 in disseminated ovarian cancer tumours following intraperitoneal administration. Shedding of the layer-by-layer coating and serum-protein-mediated extraction of IL-12-conjugated lipids from the liposomal core over time enabled IL-12 to disseminate in the tumour bed following rapid nanoparticle localization in tumour nodules.

Optimized IL-12-polymer-coated nanoparticles promoted robust T cell accumulation in ascites and tumours in mouse models, extending survival compared with free IL-12 and sensitizing tumours to immune checkpoint inhibitors, eliciting strong immune responses and immune memory.

Overall, these findings support the potential of these polymer-coated nanoparticles for the sustained delivery of IL-12 to disseminated metastatic ovarian cancer."

New nanoparticles stimulate the immune system to attack ovarian tumors | MIT News | Massachusetts Institute of Technology "Targeted particles carrying the cytokine IL-12 can jump-start T cells, allowing them to clear tumors while avoiding side effects."

IL-12-releasing nanoparticles for effective immunotherapy of metastatic ovarian cancer

Fig. 3: Mal LbL NPs efficiently target and deliver IL-12 to OC tumour nodules.

Nanoflowers rejuvenate old and damaged human cells by replacing their mitochondria

Good news! This could be huge!

"Biomedical researchers ... may have discovered a way to stop or even reverse the decline of cellular energy production—a finding that could have revolutionary effects across medicine. ...

The study ... used a combination of microscopic flower-shaped particles—called nanoflowers—and stem cells. In the presence of these nanoflowers, the stem cells produced twice the normal amount of mitochondria. When these boosted stem cells were placed near damaged or aging cells, they transferred their surplus mitochondria to their injured neighbors. ..."

From the significance and abstract:

"Significance

Mitochondrial dysfunction plays a key role in many diseases, yet treatments to restore function remain limited. Cells naturally transfer mitochondria to help repair damage, but this process is inefficient.

Here, we use molybdenum disulfide (MoS2) nanoflowers to boost mitochondrial production, turning donor cells into mitochondrial biofactories.

These cells transfer more mitochondria to damaged cells, significantly improving energy production and function. In disease models, this approach restores cell health, offering a strategy for treating mitochondrial-related disorders. By enhancing the body’s own repair mechanisms, this nanomaterial-based method could pave the way for innovative therapies in regenerative medicine.

Abstract

Intercellular mitochondrial transfer, the spontaneous exchange of mitochondria between cells, is a recently described phenomenon crucial for cellular repair, regeneration, and disease management. Enhancing this natural process holds promise for developing novel therapies targeting diseases associated with mitochondrial dysfunction.

Here, we introduce a nanomaterial-based approach employing molybdenum disulfide (MoS2) nanoflowers with atomic-scale vacancies to stimulate mitochondrial biogenesis in cells to make them mitochondrial biofactories.

Upon cellular uptake, these nanoflowers result in a two-fold increase in mitochondrial mass and enhancing mitochondrial transfer to recipient cells by several-fold.

This enhanced efficiency of transfer significantly improves mitochondrial respiratory capacity and adenosine triphosphate production in recipient cells under physiological conditions.

In cellular models of mitochondrial and cellular damage, MoS2 enhanced mitochondrial transfer achieved remarkable restoration of cell function.

This proof-of-concept study demonstrates that nanomaterial-boosted intercellular mitochondrial transfer can enhance cell survivability and function under diseased conditions, offering a promising strategy for treating mitochondrial dysfunction-related diseases."

Nanoflowers rejuvenate old and damaged human cells by replacing their mitochondria

Nanomaterial-induced mitochondrial biogenesis enhances intercellular mitochondrial transfer efficiency (open access)

Fig. 1 Synthesis and characterization of size-tunable MoS2 nanoflowers.

Fig. 2 Treatment with MoS2 nanoflowers stimulates mitochondrial biogenesis and bioenergetics.

Pollen-like micromotors fly through the air using light and heat

Amazing stuff! The first article below seems to be short summary of recent developments.

"For the first time, researchers have created micromotors that can move through the air in a controlled way powered only by light.

The findings pave the way for new microscale technologies that transport nanoparticles through the air for applications in catalysis and the environment.

The spiky, pollen-like zinc oxide microparticles are coated with gold nanoparticles which heat up when exposed to near-infrared light.

Researchers can control the temperature gradient in the micromotor by changing the direction of the incoming light. This creates gentle convection currents that lift and push the micromotor into the air in a steerable way.

Micromotors are materials inspired by nature that move in controlled ways in response to chemical reactions or other external stimuli.

These tiny moving motors work well in liquid environments where fluid supports the particles while facilitating heat dissipation and convective motion. But flying micromotors through the air, where the force of gravity works against them, has remained a major challenge. ..."

"... researchers has developed the first micromotors capable of moving through the air using only light as their power source. These tiny, pollen-shaped particles measure about 12 microns wide — roughly one-tenth the thickness of a human hair. Made of zinc oxide and coated with gold, they use heat from near-infrared light to lift and propel themselves without any fuel or batteries.

When a beam of light strikes the micromotors, the gold absorbs energy and heats the surrounding air. This heat creates gentle convection currents — like rising warm air — that push the particles upward and allow them to move in controlled directions. By adjusting the position of the light, the researchers can steer their motion. ..."

From the abstract:

"Micromotors are an attractive cutting-edge technology that exhibit controllable motion in response to chemical reactions or external stimuli.

These nature-inspired materials are widely explored for use in environmental remediation, and drug delivery, other emerging applications.

Until now, the micromotors field is restricted to applications in aqueous environments, as achieving controllable motion in air while overcoming gravity remains a significant challenge.

Herein, for the first time, to our knowledge, we introduce a system capable of overcoming gravity to achieve light-induced thermal convective motion in air, driven by near-infrared light excitation.

The micromotors are composed of spiky, pollen-like ZnO microparticles coated with gold nanoparticles, which interact photothermally with the NIR light, generating a thermal gradient that induces propulsion of the micromotor system. Lanthanide-doped upconverting nanoparticles are deposited onto the micromotor surface to enable nanothermometric monitoring of surface temperature, providing critical information needed to describe the system's thermal behavior in air. This micromotor platform provides a versatile approach to overcome gravity and induce a controllable movement in a gaseous matrix, opening new opportunities to develop proof-of-concepts and applications using this aerodynamic micromotor approach."

Pollen-like micromotors fly using light and heat | News | ConnectSci

Concordia researchers develop light-powered micromotors that move through air (original news release) "Tiny, gold-coated particles can lift and steer themselves using heat from near-infrared light"

Light-Activated Micromotors in Air Propelled by Thermal Convection (open access)

Fig. 1 A) Scheme illustrating i) micromotor assembly, and ii) NIR-light driven motion of micromotors in air by induced photophoresis.

B) SEM micrographs of ZnO─Au─UCNPs micromotors with their corresponding EDS elemental mapping images for Zn, O, Au, and Gd. Scale bar is 10 µm. Schematic was created using BioRender.

Fig. 3 Motion mechanism determination of the micromotors in air under 808 nm excitation.

Micromotor cluster closeup.

Membrane extracts lithium with precise selectivity and minimal environmental impact

Good news!

"A new membrane marks an important step toward more efficient extraction of lithium which is needed for reusable batteries. The design can also be used to extract other essential elements like cobalt and nickel. ...

The membrane developed by the team extracts lithium using considerably less energy, while maintaining higher selectivity. 

The membrane collects lithium through a process called electrodialysis. An electrical current is applied to the brine which pushes lithium ions to pass through the membrane, whilst other elements like sodium, calcium and magnesium get left behind. ...

The team were able to create such an effective membrane by inserting nanoparticles of lithium titanium oxide (LTO) into it. The crystal structure of LTO is the perfect size for lithium ions to move across without allowing for other elements to pass through. ..."

"... the researchers demonstrated near-perfect lithium selectivity by repurposing solid-state electrolytes (SSEs) as membrane materials for aqueous lithium extraction. While originally designed for the rapid conduction of lithium ions in solid-state batteries — where there are no other ions or liquid solvents — the highly ordered and confined structure of SSEs was found to enable unprecedented separation of both ions and water in aqueous mixtures. ..."

From the abstract:

"Precise separation of ions of the same polarity and similar valence and size remains a critical need in resource recovery from waste streams. Here, we report the rational design and scalable fabrication of a thin film nanocomposite (TFN) cation exchange membrane to achieve precise selectivity for lithium over competing cations.

The precise selectivity is realized by an ultrathin polyamide (PA) layer incorporated with amine functionalized β-monoclinic lithium titanium oxide (N-LTO) nanoparticles using a scalable interfacial polymerization process that allows high N-LTO loading while minimizing interfacial defects.

The TFN membrane demonstrates superior Li+ permeability, with Li+/Ca2+ and Li+/Na+ selectivity reaching 173.90 and 13.58, respectively. The Li+/Na+ selectivity is attributed to the Li+-exclusive transport pathway in the layered structure of the N-LTO, while size exclusion by the highly cross-linked N-LTO-PA also contributes to the Li+/Ca2+ selectivity.

Molecular dynamics simulation shows that the electrical field drives Li+ dehydration and accelerates the migration of the dehydrated Li+ while Na+ is blocked due to its larger size than the Li+ cavity. The high Li+ selectivity and permeability enable energy-efficient, precise, and chemical-free lithium extraction using the electrodialysis process. The TFN membrane architecture also allows simple and scalable fabrication of a multi-functional polymer-inorganic nanocomposite membrane."

Membrane extracts lithium with minimal environmental impact

Rice researchers develop efficient lithium extraction method, setting stage for sustainable EV battery supply chains (original news release) "Solid-state electrolyte membranes revolutionize lithium harvesting with near-perfect selectivity"

A rationally designed scalable thin film nanocomposite cation exchange membrane for precise lithium extraction (open access)

Fig. 1: TFN-CEM with high and uniform loading of N-LTO.

Nanoparticles detect and reduce artery plaques

Good news!

"A new generation of “theranostic” nanoparticles has been shown to both detect and reduce plaques in the arteries. Nanoparticles absorbed by immune cells in the arteries, where they work to lower inflammation and draw out harmful cholesterol, offer an entirely new way of not just diagnosing but fighting heart disease without drugs. ..."

"... The study used advanced imaging techniques to track the movement of the nanoparticles in pre-clinical models of heart disease. They were able to target inflamed plaques and significantly reduce both plaque size and inflammation.

"One of the key challenges in treating atherosclerosis is that inflammation fuels plaque build-up, creating a vicious cycle. Our nanoparticles help break that cycle, which could lead to better long-term outcomes for patients,” ...

In addition to their ability to shrink plaques, the nanoparticles have powerful imaging capabilities that allow for earlier detection of arterial disease. This could help cardiologists identify at-risk patients sooner and intervene with treatments before complications arise. ..."

From the highlights and abstract:

"Highlights

• Atherosclerosis is the deposition of fatty plaques in arteries and the main cause of heart attacks.

• Strategies to improve detection and reduce atherosclerotic plaques are needed.

• Multifunctional porphyrin-lipid nanoparticles (Por-NPs) have diagnostic and therapeutic properties.

• Por-NPs are internalized by macrophages and track to atherosclerotic plaques, visualized using multiple imaging modalities.

• Por-NPs exert atheroprotective effects in vitro in macrophages. They suppress inflammation and promote cholesterol efflux.

• Por-NPs exhibit therapeutic effects in two murine models of atherosclerosis and significantly reduce plaque size.

Abstract

Background

Porphyrin-lipid nanoparticles (Por-NPs) have unrealized potential for atherosclerosis. Por-NPs incorporate porphyrin-lipid which permits fluorescence imaging and chelates Copper-64 (64Cu) for positron emission tomography (PET) imaging. Their outer shell contains a short peptide ‘R4F’ that enables macrophage targeting and therapeutic effects. Accordingly, this study investigates the simultaneous diagnostic and therapeutic properties of Por-NPs in atherosclerosis.

Results

In vitro, Por-NPs were found to be internalized by immortalised bone marrow-derived macrophages (iBMDMs), visualized via fluorescence microscopy and flow cytometry.

Por-NPs also increased cholesterol efflux from [3H]-cholesterol-loaded iBMDMs, (49 %, P < 0.05).

Incubation of iBMDMs with Por-NPs reduced mRNA levels of inflammatory mediators Il1b (88 %), Il18 (54 %) Ccl5 (75 %) and Ccl17 (92 %), and protein secretion of IL-1β (69 %), CCL5 (82 %) and CCL17 (94 %), P < 0.05. Por-NPs suppressed inflammasome components Nlrp3 (69 %) and Asc (36 %), P < 0.05. Studies using siRNA deletion of SR-B1 and methyl-β-cyclodextrin, revealed the anti-inflammatory properties of Por-NPs were independent of SR-B1 and cholesterol efflux. However, Por-NPs suppressed activation of inflammatory transcription factor NF-κB (53 %, P < 0.05).

In vivo, in Apoe−/− mice, serial non-invasive PET imaging showed 64Cu-labelled Por-NPs localised in hearts and detected increases in plaque size longitudinally with high-cholesterol diet. Por-NP fluorescence was visualized in aortic sinus plaques, co-localised with CD68+ macrophages, and by fluorescence IVIS imaging in aortic arch plaque.

In two murine models, Por-NP-treated mice had smaller early-stage (22 %) and unstable plaques (52 %). Por-NP-treated mice had fewer circulating (32 %) and aortic (81 %) monocytes, and lower mRNA levels of aortic arch Rela (26 %) and Nfkb1 (27 %), P < 0.05.

Conclusions

Por-NPs detect plaques using multiple imaging modalities and exhibit atheroprotective effects, presenting as novel nanoscale theranostics for atherosclerosis."

Nanoparticles detect and reduce artery plaques

Nanoparticles engineered to suck the plaque out of arteries (original news release) "Researchers at SAHMRI are using specially designed nanoparticles to detect and help treat plaque build-up in arteries for the first time, offering a potential new approach to diagnosing and managing heart disease."

Theranostic porphyrin nanoparticles identify atherosclerosis via multimodal imaging and elicit atheroprotective effects (open access)

Graphical abstract

The durable cure for cystic fibrosis might start in the womb

Good news!

"... Using in utero gene editing, the researchers developed a method to deliver corrective genetic material to the fetus of mice with CF via tiny particles called nanoparticles. ...

Cystic fibrosis arises from mutations in the CF transmembrane conductance regulator, or CFTR. Because the disease is caused by a single mutation, researchers saw it as a great candidate for gene editing, specifically in utero gene editing.  ...

In the study, researchers used synthetic molecules similar to DNA — called peptide nucleic acids, or PNAs — to correct CFTR. PNA can be tweaked to bind to a particular gene containing a mutation in a strand of DNA, which can cause a lesion that the cell then removes itself. The gene is then corrected when a strand of DNA without the mutation takes its place. ...

The researchers delivered the PNA to the fetuses of mice using tiny synthetic particles called nanoparticles, which are the same size as viruses to correct the CFTR mutation before the mice were born. ..."

From the significance and abstract:

"Significance

Cystic fibrosis (CF), a monogenic disease resulting from mutations in the CF transmembrane conductance regulator (CFTR) gene, affects multiple organs, including the respiratory, gastrointestinal, and reproductive systems.

Irreversible pathology in these tissues is often already present at birth, suggesting that a true curative therapy would require intervention during fetal development.

Here, we demonstrate CFTR gene correction in multiple tissues affected by CF after a single in utero administration of nanoparticles containing gene editing cargo. We found that gene correction was durable into adulthood in mice, which resulted in functional CFTR activity in both the respiratory and gastrointestinal systems. Our work establishes the possibility that CF could be treated, or possibly cured, by a single in utero gene editing treatment.

Abstract

In utero gene editing has the potential to modify disease-causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. 

In cystic fibrosis (CF), a disease that arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. 

Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage. Here, we demonstrate proof-of-concept of multiorgan mutation correction in CF using peptide nucleic acids encapsulated in polymeric nanoparticles and delivered systemically in utero.

In utero editing was associated with sustained postnatal CFTR activity, at a level similar to that of wild-type mice, in both respiratory and gastrointestinal tissues, without detection of off-target mutations in partially homologous loci. This work suggests that systemic in utero gene editing represents a viable strategy for treating monogenic diseases before birth that impact multiple tissue types."

The cure for cystic fibrosis might start in the womb | Yale News "In a new study, Yale researchers develop a method that has the potential to cure cystic fibrosis prior to birth."

Systemic in utero gene editing as a treatment for cystic fibrosis (no public access)

Marie Egan, a senior author of the study

New vaccine shows promise against pancreatic cancer in preclinical studies

Good news! Cancer is history soon! This research still seems to be in early stage, the details seem sketchy and no published results.

"... The pioneering work from ... researchers targets pancreatic ductal adenocarcinoma (PDAC), the most common cancer that plagues the organ. While pancreatic cancer may not be as prevalent as breast, prostate, lung and colorectal cancers, it's particularly insidious. It commonly remains undetected until it metastasizes, and then treatment is simply to buy more time. The five-year survival rate for this cancer is just 13.3%. ...

The treatment centers around targeting the most common mutations seen in PDAC tumor cells, using nanoparticles loaded with antigens that trigger the immune system to attack and destroy the cancer growth. In preclinical trials, which generally test novel treatments on isolated cell cultures or animals, the vaccine eliminated the cancer in more than half of the targets. ...

Treatment would involve three injections of the anti-cancer nanoparticles, with a complementary immune checkpoint inhibitor to boost the body's tumor-fighting capabilities, limiting the ability of tumors to evade immune cell detection. ...

The institution is yet to publish new research on the vaccine, but is expected to release data once preclinical trials have concluded. ..."

New vaccine shows promise against pancreatic cancer

Pancreatic cancer vaccines eliminate disease in preclinical studies "Case Western Reserve University researchers combat deadly cancer with therapeutic vaccines"

Anticancer ELNP nanovaccines for curative treatment of pancreatic cancer

Nanoparticles demonstrate new and unexpected mechanism of coronavirus disinfection

Amazing stuff! I bet it applies not only to coronavirus!

"... One promising approach relies on the use of nanoparticles, with several metal and metal oxide nanoparticles showing anti-viral activity against SARS-CoV-2, the virus that causes COVID-19. With this in mind, researchers ... investigated the effect of such nanoparticles on two different virus types.

Aiming to elucidate the nanoparticles’ mode of action, they discovered a previously unknown antiviral mechanism ..."

"... It should also be easy to design cost-effective filters to purify contaminated air and water,” ...

Now, researchers ... have studied the outcome when certain types of mineral nanoparticles come into contact with a coronavirus, and they discovered a mode of action that has not been proposed before. ...

Coronaviruses belong to a type of virus that has an outer envelope, a lipid membrane. It turned out that nanoparticles of sand minerals such as titanium oxide bind very strongly to phospholipids in this membrane. This damages the membrane and leads to the release of viral genetic material, thereby making the virus less able to infect cells. ..."

From the abstract:

"The recent COVID-19 pandemic has set a strong quest for advanced understanding of possible tracks in abating and eliminating viral infections. In the view that several families of “pristine” small oxide nanoparticles (NPs) have demonstrated viricidal activity against SARS-CoV-2, we studied the effect of two NPs, with presumably different reactivity, on two viruses aiming to evaluate two “primary suspect” routes of their antiviral activity, either specific blocking of surface proteins or causing membrane disruption.

The chosen NPs were non-photoactive 3.5 nm triethanolamine terminated (surface capped) titania TiO2 NPs (TATT) and ultrasmall (1.1 nm) silicotungstate polyoxometalate (POM) NPs. The former were expected to both, interact with viral surface proteins as well as strongly complex with phosphate groups whereas the latter was not expected to form surface complexes.

We demonstrated that expectedly, POM NPs up to 1.25 mM (4.5 mg l−1) had no significant antiviral activity towards neither of the used viruses, an enveloped transmissible gastroenteritis virus (TGEV) belonging to coronaviruses and non-enveloped encelomyocarditis virus (EMCV).

At the same time, TATT NPs exhibited statistically significant (p < 0.05) antiviral activity against TGEV starting from 0.125 mM (12 μg ml−1). However, no antiviral activity of TATT against non-enveloped EMCV was detected. The observation that TATT NPs showed activity only against enveloped viruses and at relatively high concentrations suggests that the effect could be related with complexation with phospholipids. Possible chemical mechanism of viral membrane disruption was investigated by a variable temperature NMR study of NP complexation with model organic phosphate molecules, proving TATT to strongly interact with them and POM remain unreacted. Viral membrane disruption by TATT NPs was additionally confirmed by demonstrating RNA leakage from TGEV upon contact with those NPs. Therefore, our study proved a new mechanism of antiviral action of titania NPs in the dark which involved membrane disruption proceeding via direct surface complexation."

Nanoparticles demonstrate new and unexpected mechanism of coronavirus disinfection – Physics World

Nanoparticles damage coronavirus in an unexpected way, paving the way for new disinfection technology (original news release) "A new way to neutralise the coronavirus and other membrane-surrounded viruses has been discovered by researchers from the Swedish University of Agricultural Sciences and the University of Tartu. Certain mineral nanoparticles were found to damage the membrane of the virus, making it less able to enter human cells. The mode of action that is demonstrated has not been discussed in previous research. The technology works at room temperature and also in the dark, offering a range of benefits for disinfecting surfaces, air and water."

Molecular mechanisms behind the anti corona virus activity of small metal oxide nanoparticles (open access)

Fig. 8 Proposed schematics of the interaction between enveloped virus and TATT TiO2/TATT/TATT titanate nanoparticles (grey color indicates phospholipids, yellow and brown indicate different kinds of membrane proteins).

Gold nanoparticles outperform common weight loss drugs – and leaves muscles alone

Good news!

"There's a growing body of evidence that gold nanoparticles can offer significant, targeted weight loss that focuses on fat (lipid) tissue, without affecting muscle structure. What's more, there are added health bonuses, including anti-inflammatory properties and improvements in blood glucose levels. ...

The numbers are impressive – 36% targeted fat loss over nine weeks, compared to the typical 10-20% reduction of body weight seen in those taking GLP-1 drugs (with up to 20% of that being muscle loss) – yet so far the scientists have only conducted animal studies. This research, however, gets the novel obesity treatment a step closer to a human trial. ..."

From the abstract:

"Obesity is a metabolic disease characterized by an imbalance between caloric intake and expenditure, leading to excess fat and increasing the risk of various health conditions.

This study compares the anti-obesity effects of gold nanoparticles (AuNPs) to orlistat in an experimental model of induced obesity in Wistar Albino rats. In addition to negative and positive control rats, obese rats were treated with variable daily and weekly doses of AuNPs and daily orlistat for nine weeks. Bioelectric impedance analysis (BIA) and dissection techniques were used to indirectly and directly measure body-composition in all rat groups. Hepatic and renal function and ultrastructure were assessed by blood biochemical and histological examinations to detect treatment-related alterations.

High doses of AuNPs reduced body fat, increased muscle mass, improved dyslipidemia, glycemia, and antioxidant effects in obese rats, and restored normal TG, FBG, and MDA levels by reducing obesity-related oxidative damage.

Histological and ultrastructural examinations showed that these high doses repaired liver and kidney cells, and reduced fat accumulation and body weight compared to the standard treatment for obesity by orlistat."

Gold outperforms common weight loss drugs – and leaves muscles alone

Effect of gold nanoparticles treatment on rats-induced obesity by evaluating body-composition directly and indirectly via bioelectric impedance analysis (open access)

New approach to genetic modification wipes years off genetic trials for plants

Good news!

"Researchers have for the first time introduced genetic material into plants via their roots, the trials opening a potential pathway for rapid crop improvement. ...

nanoparticle technology could help fine-tune plant genes to increase crop yield and improve food quality. ...

The nanoparticle technique has been patented by [University of Queensland’s] commercialisation company UniQuest, which is now seeking partners to further develop the technology. ..."

From the abstract:

"Nanoparticle-mediated delivery of nucleic acids and proteins into intact plants has the potential to modify metabolic pathways and confer desirable traits in crops.

Here we show that layered double hydroxide (LDH) nanosheets coated with lysozyme are actively taken up into the root tip, root hairs and lateral root junctions by endocytosis, and translocate via an active membrane trafficking pathway in plants.

Lysozyme coating enhanced nanosheet uptake by

(1) loosening the plant cell wall and

(2) stimulating the expression of endocytosis and other membrane trafficking genes.

The lysozyme-coated nanosheets efficiently delivered synthetic mRNA, double-stranded RNA, small interfering RNA and plasmid DNA up to 15 kb in size into tobacco roots, and also functional nucleic acids into leaves, callus, flowers and developing pollen of dicot and monocot species. Thus, lysozyme-coated LDH nanoparticles are a versatile tool for efficiently delivering functional nucleic acids into plants."

New approach wipes years off genetic trials

Lysozyme-coated nanoparticles for active uptake and delivery of synthetic RNA and plasmid-encoded genes in plants (no public access)

Nanoparticle infusion therapy breaks down plaques in arteries to treat atherosclerosis

Good news!

"... For the new study, the team used CD47-blocking nanoparticles that are more targeted towards monocytes and macrophages, two types of immune cell that are associated with inflammation in plaques. And sure enough, in tests in pigs the therapy reduced atherosclerosis as effectively as previous drugs, without any damage to blood cells. ..."

"... Earlier studies in mice required hundreds of microliters of the nanotherapy infusion but, most recently, ... team have achieved measurable impact in pigs by scaling up the amount produced to liters. These volumes are in the range needed for human use. This study represents a critical step toward translation to patient clinical trials of safer, more effective cardiovascular therapies."

From the abstract:

"Atherosclerosis is an inflammatory disorder responsible for cardiovascular disease. Reactivation of efferocytosis, the phagocytic removal of cells by macrophages, has emerged as a translational target for atherosclerosis. Systemic blockade of the key ‘don’t-eat-me’ molecule, CD47, triggers the engulfment of apoptotic vascular tissue and potently reduces plaque burden. However, it also induces red blood cell clearance, leading to anemia. To overcome this, we previously developed a macrophage-specific nanotherapy loaded with a chemical inhibitor that promotes efferocytosis. Because it was found to be safe and effective in murine studies, we aimed to advance our nanoparticle into a porcine model of atherosclerosis. Here, we demonstrate that production can be scaled without impairing nanoparticle function. At an early stage of disease, we find our nanotherapy reduces apoptotic cell accumulation and inflammation in the atherosclerotic lesion. Notably, this therapy does not induce anemia, highlighting the translational potential of targeted macrophage checkpoint inhibitors."

Nanoparticle infusion therapy breaks down plaques in arteries

MSU research advances infusion designed to clean arteries (original news release)

Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis (open access)

L-R: Plaque levels in an artery before and after the nanotherapy infusion

Fig. 4: Pro-efferocytic therapies induce favorable immunological gene expression changes across species.