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In Biopharma, Tiny Carbon Dots Mean Big Opportunities

Crossing the blood-brain barrier is a familiar challenge in therapeutic applications. And it is increasingly recognized as a challenge for imaging applications,…



Crossing the blood-brain barrier is a familiar challenge in therapeutic applications. And it is increasingly recognized as a challenge for imaging applications, too. In the not-too-distant future, therapeutic and imaging applications may be better able to overcome this challenge—provided new, enabling technologies perform as hoped. One such technology is carbon nanoparticle technology.

Carbon nanoparticles, which have a core-shell structure and a diameter of less than 10 nm, exhibit several useful properties. They include ultra-small size, tunable photoluminescence, various surface functionalities, high water dispersibility, and biocompatibility. By exploiting these properties, a small company named C-Dots Nanotech is working to improve drug delivery and bioimaging.

Neuron targeting for imaging

“We have specific types of carbon nanoparticles, called C-Dots, that target neurons,” says Elif S. Seven, PhD, senior scientist and production manager, C-Dots Nanotec. “The C-Dots cross the blood-brain barrier and accumulate in the neurons,” enabling imaging applications. The alternative is to use dyes; however, relatively few dyes are suitable for in vivo or in vitro imaging.

Seven also suggests how C-Dots may facilitate drug delivery. “We can deliver small molecules to neurons in a nonviral way,” she tells GEN. According to Seven, the immune response stimulated by the technique is minimal or undetectable.

C-Dots may prove especially useful in the delivery of cancer drugs. “We can customize the drug delivery platform by attaching targeting ligands to the C-Dots along with chemotherapy drugs (singly or in combination) for precise targeting,” Seven explains. “We have shown that when two different chemotherapy drugs are conjugated to C-Dots along with transferrin, there is a synergistic anticancer effect on glioblastoma cell lines.” C-Dots Nanotec has been working in-house with glioblastomas and neuroblastomas, and it has identified the types of C-Dots that work best for certain scenarios. The company also works with external researchers to develop carbon dots for other cancers.

Seven notes that in a recent study for neuroblastoma, a specific type of C-Dot was identified that showed a “significant, intrinsic anticancer property while being minimally toxic to healthy cell lines.” When C-Dots Nanotec tested the C-Dots against seven or eight cancer cell lines, the company found that the C-Dots killed one cell line that had a specific mutation. Additional studies to explore that capability are being planned.

Nanodots aren’t quantum dots

While C-Dots Nanotec’s technology looks promising, the company’s work is still in the preclinical stage. That’s par for the industry. Despite being discovered some two decades ago as a product of carbon nanotube synthesis, carbon nanodots generally are underrecognized in the biopharmaceutical world.

Carbon nanodots developed by C-Dots Nanotec are highly photoluminescent. In addition, they can be tuned for blue, red, green, and yellow photoluminescence, as well for intermediate colors. In these images, water dispersions of the company’s carbon nanodots are shown under room light (left) and under ultraviolet light (right).

“Carbon nanodots are often confused with quantum dots,” Seven points out. “Carbon nanodots are spherical nanoparticles with a diameter of less than 10 nanometers. Even in the nanoparticle world, that’s very small. And unlike quantum dots, carbon nanodots don’t have toxic metals such as cadmium.”

Carbon nanodots exhibit stability and low toxicity. Also, as mentioned earlier, they are both highly biocompatible and highly photoluminescent. They can be tuned for blue, red, green, or yellow photoluminescence—or “anything in between,” Seven remarks. Typically, citric acid and urea are the precursors, and adding nitrogen enhances the carbon nanodots’ luminescence.

“There are two general types of synthesis: top-down and bottom-up,” Seven continues. “We can use small molecules to build the dots from the bottom-up. For top-down, we use larger carbon-based particles to cut down to make the dots.”

She also explains how C-Dots can be given different targeting properties that can enhance drug delivery: “Especially for the small molecules, the composition of the surface functional groups may be different based on their precursors. For example, C-Dots made from folic acid target the folic acid receptor, and C-Dots made from glucose enter cells using glucose transporter proteins. So, they sometimes take on the properties of their precursors. That’s why they can target specific cells.”

High levels of biocompatibility and the ability of these carbon dots to go places other modalities cannot reach easily are expanding their potential applications. Besides having the potential to target brain cancers and neurodegenerative diseases, C-Dots may be able to target pancreatic cancer and dermatology conditions. And C-Dots Nanotec may pursue additional applications by participating in collaborations.

C-Dots Nanotec is one of only a few companies developing these carbon nanodots. This observation, Seven reports, has been confirmed by C-Dots Nanotec’s competitive research. She adds that some competitors’ products more closely resemble dyes than carbon dots, based upon spectra and other product characteristics.

She declares that C-Dots Nanotec can offer high purity levels and “guarantee batch-to-batch reproducibility.” Accordingly, researchers can run experiments with one batch of C-Dots and then reproduce their results by running experiments with C-Dots from other batches.

Focusing on carbon nanodots

C-Dots Nanotec was founded in 2019 as a sister company to C-Dots, which was founded in 2017. Both companies were co-founded by Roger M. LeBlanc, PhD, a professor of chemistry at the University of Miami. He has developed multiple companies around carbon nanodots, including those for neuro-oncology and neurodegenerative diseases, and others for dermatology, fuel additives, and R&D. The dots also have agricultural applications.

“When we started C-Dots Nanotec a few years ago, there were not many companies offering carbon dots, so we are probably first in the market,” Seven says. “We really believe carbon dots are unique.”

Now, C-Dots Nanotec is working with academic partners at the University of Florida, the University of Miami, and the University of Iowa, and it is also interested in working with corporate partners.

Incorporating carbon nanodots into a research program is as straightforward as chemically conjugating them with a program’s small-molecule drugs and/or peptides and then measuring their effects on delivery efficiency. “Carbon dots are like catalysts,” Seven says. “As additives, they have been shown to increase efficiency.”

Seven looks forward to pursuing applications in two exciting fields: “One, of course, is neurology, with neurodegenerative diseases and oncology as part of that. The second is jet fuel.” Applications that improve fuel efficiency could have an impact and generate revenue relatively quickly.

Thriving in a new niche

The carbon nanodot industry is still in its infancy. “If you’re not in the field,” Seven admits, “there’s a high chance you have never heard of carbon nanodots.” They may be overlooked by researchers in need of delivery technologies. Indeed, researchers typically opt for more familiar technologies, such as those based on polymers or liposomes.

Seven recognizes that creating a new market will be challenging. Nonetheless, she emphasizes that “more suppliers and more companies are adding carbon dots to their product lines.”

Being located in Florida, away from the conventional biopharmaceutical hubs, is an additional challenge. The location issue was evident when C-Dots Nanotec participated in a startup workshop at the Massachusetts Institute of Technology. “The vibe was so high and energetic,” Seven recalls. “We did a lot [with researchers], but we may have done a lot more if we had been a Boston-based company.” Worse, travel has been limited by the pandemic, she says. This year, C-Dots Nanotec is renewing its efforts to form collaborations that may help the company transition from laboratory work to clinical trials.

The post In Biopharma, Tiny Carbon Dots Mean Big Opportunities appeared first on GEN - Genetic Engineering and Biotechnology News.

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Lower mortgage rates fueling existing home sales

To understand why we had such a beat in sales, you only need to go back to Nov. 9, when mortgage rates started to fall from 7.37% to 5.99%.



Existing home sales had a huge beat of estimates on Tuesday. This wasn’t shocking for people who follow how I track housing data. To understand why we had such a beat in sales, you only need to go back to Nov. 9, when mortgage rates started to fall from 7.37% to 5.99%.

During November, December and January, purchase application data trended positive, meaning we had many weeks of better-looking data. The weekly growth in purchase application data during those months stabilized housing sales to a historically low level.

For many years I have talked about how rare it is that existing home sales trend below 4 million. That is why the historic collapse in demand in 2022 was one for the record books. We understood why sales collapsed during COVID-19. However, that was primarily due to behavior changes, which meant sales were poised to return higher once behavior returned to normal.

In 2022, it was all about affordability as mortgage rates had a historical rise. Many people just didn’t want to sell their homes and move with a much higher total cost for housing, while first-time homebuyers had to deal with affordability issues.

Even though mortgage rates were falling in November and December, positive purchase application data takes 30-90 days to hit the sales data. So, as sales collapsed from 6.5 million to 4 million in the monthly sales data, it set a low bar for sales to grow. This is something I talked about yesterday on CNBC, to take this home sale in context to what happened before it. 

Because housing data and all economics are so violent lately, we created the weekly Housing Market Tracker, which is designed to look forward, not backward.

From NAR: Total existing-home sales – completed transactions that include single-family homes, townhomes, condominiums and co-ops – vaulted 14.5% from January to a seasonally adjusted annual rate of 4.58 million in February. Year-over-year, sales fell 22.6% (down from 5.92 million in February 2022).

As we can see in the chart above, the bounce is very noticeable, but this is different than the COVID-19 lows and massive rebound in sales. Mortgage rates spiked from 5.99% to 7.10% this year, and that produced one month of negative forward-looking purchase application data, which takes about 30-90 days to hit the sales data.

So this report is too old and slow, but if you follow the tracker, you’re not slow. This is the wild housing action I have talked about for some time and why the Housing Market Tracker becomes helpful in understanding this data.

The last two weeks have had positive purchase application data as mortgage rates fell from 7.10% down to 6.55%; tomorrow, we will see if we can make a third positive week. One thing to remember about purchase application data since Nov. 9, 2022 is that it’s had a lot more positive data than harmful data. 

However, the one-month decline in purchase application data did bring us back to levels last seen in 1995 recently. So, the bar is so low we can trip over.

One of the reasons I took off the savagely unhealthy housing market label was that the days on the market are now above 30 days. I am not endorsing, nor will I ever, a housing market that has days on the market at teenager levels. A teenager level means one of two bad things are happening:

1. We have a massive credit boom in housing which will blow up in time because demand is booming, similar to the run-up in the housing bubble years.

2. We simply don’t have enough products for homebuyers, creating forced bidding in a low-inventory environment. 

Guess which one we had post 2020? Look at the purchase application data above — we never had a credit boom. Look at the Inventory data below. Even with the collapse in home sales and the first real rebound, total active listings are still below 1 million.

From NAR: Total housing inventory registered at the end of February was 980,000 units, identical to January & up 15.3% from one year ago (850,000). Unsold inventory sits at a 2.6-month supply at the current sales pace, down 10.3% from January but up from 1.7 months in February ’22. #NAREHS

However, with that said, the one data line that I love, love, love, the days on the market, is over 30 days again, and no longer a teenager like last year, when the housing market was savagely unhealthy.

From NAR: First-time buyers were responsible for 27% of sales in January; Individual investors purchased 18% of homes; All-cash sales accounted for 28% of transactions; Distressed sales represented 2% of sales; Properties typically remained on the market for 34 days.

Today’s existing home sales report was good: we saw a bounce in sales, as to be expected, and the days on the market are still over 30 days. When the Federal Reserve talks about a housing reset, they’re saying they did not like the bidding wars they saw last year, so the fact that price growth looks nothing like it was a year ago is a good thing.

Also, the days on market are on a level they might feel more comfortable in. And, in this report, we saw no signs of forced selling. I’ve always believed we would never see the forced selling we saw from 2005-2008, which was the worst part of the housing bubble crash years. The Federal Reserve also believes this to be the case because of the better credit standards we have in place since 2010. 

Case in point, the MBA‘s recent forbearance data shows that instead of forbearance skyrocketing higher, it’s collapsed. Remember, if you see a forbearance crash bro, hug them, they need it.

Today’s existing home sales report is backward looking as purchase application data did take a hit this year when mortgage rates spiked up to 7.10%. We all can agree now that even with a massive collapse in sales, the inventory data didn’t explode higher like many have predicted for over a decade now.

I have stressed that to understand the housing market, you need to understand how credit channels work post-2010. The 2005 bankruptcy reform laws and 2010 QM laws changed the landscape for housing economics in a way that even today I don’t believe people understand.

However, the housing market took its biggest shot ever in terms of affordability in 2022 and so far in 2023, and the American homeowner didn’t panic once. Even though this data is old, it shows the solid footing homeowners in America have, and how badly wrong the extremely bearish people in this country were about the state of the financial condition of the American homeowner.

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SVB contagion: Australia purportedly asks banks to report on crypto

Australia’s prudential regulator has purportedly told banks to improve reporting on crypto assets and provide daily updates.



Australia’s prudential regulator has purportedly told banks to improve reporting on crypto assets and provide daily updates.

Australia’s prudential regulator has purportedly asked local banks to report on cryptocurrency transactions amid the ongoing contagion of Silicon Valley Bank’s (SVB) collapse.

The Australian Prudential Regulation Authority (APRA) has started requesting banks to declare their exposures to startups and crypto-related companies, the Australian Financial Review reported on March 21.

The regulator has ordered banks to improve their reporting on crypto assets and provide daily updates to the APRA, the Financial Review notes, citing three people familiar with the matter. The agency is aiming to obtain more information and insight into banking exposures into crypto as well as associated risks, the sources said.

The new measures are apparently part of the APRA’s increased supervision of the banking sector in the aftermath of recent massive collapses in the global banking system. On March 19, UBS Group agreed to buy its ailing competitor Credit Suisse for $3.2 billion after the latter collapsed over the weekend. The takeover became one of the latest failures in the banking industry following the collapses of SVB and Silvergate.

Barrenjoey analyst Jonathan Mott reportedly told clients in a note that the situation “remains stable” for Australian banks but warned confidence could be quickly disrupted, putting pressure on bank margins.

Related: Silvergate, SBV collapse ‘definitely good’ for Bitcoin, Trezor exec says

“Our channel checks indicate deposits are not being withdrawn from smaller institutions in any size, and capital and liquidity buffers are strong,” Mott said, adding:

“But this is a crisis of confidence and credit spreads and cost of capital will continue to rise. At a minimum, this will add to the margin pressure the banks are facing, while credit quality will continue to deteriorate.”

The news comes soon after the Australian Banking Association launched a cost of living inquiry to study the impact of the COVID-19 pandemic and geopolitical tensions on Australians. The inquiry followed an analysis of the rising inflation suggesting that more than 186 banks in the United States are at risk of a similar shutdown if depositors decide to withdraw all funds.

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Delta Move Is Bad News For Southwest, United Airlines Passengers

Passengers won’t be happy about this, but there’s nothing they can do about it.



Passengers won't be happy about this, but there's nothing they can do about it.

Airfare prices move up and down based on two major things -- passenger demand and the cost of actually flying the plane. In recent months, with covid rules and mask mandates a thing of the past, demand has been very heavy.

Domestic air travel traffic for 2022 rose 10.9% compared to the prior year. The nation's air traffic in 2022 was at 79.6% of the full-year 2019 level. December 2022 domestic traffic was up 2.6% over the year-earlier period and was at 79.9% of December 2019 traffic, according to The International Air Transport Association (IATA).

“The industry left 2022 in far stronger shape than it entered, as most governments lifted COVID-19 travel restrictions during the year and people took advantage of the restoration of their freedom to travel. This momentum is expected to continue in the New Year,” said IATA Director General Willie Walsh.

And, while that's not a full recovery to 2019 levels, overall capacity has also not recovered. Total airline seats available actually sits "around 18% below the 2019 level," according to a report from industry analyst OAG.

So, basically, the drop in passengers equals the drop in capacity meaning that planes are flying full. That's one half of the equation that keeps airfare prices high and the second one looks bad for anyone planning to fly in the coming years.

Image source: Getty Images.

Airlines Face One Key Rising Cost

While airlines face some variable costs like fuel, they also must account for fixed costs when setting airfares. Personnel are a major piece of that and the pandemic has accelerated a pilot shortage. That has given the unions that represent pilots the upper hand when it comes to making deals with the airlines.

The first domino in that process fell when Delta Airlines (DAL) - Get Free Report pilots agreed to a contract in early March that gave them an immediate 18% increase with a total of a 34% raise over the four-year term of the deal.

"The Delta contract is now the industry standard, and we expect United to also offer their pilots a similar contract," investment analyst Helane Becker of Cowen wrote in a March 10 commentary, Travel Weekly reported.

US airfare prices have been climbing. They were 8.3% above pre-pandemic levels in February, according to Consumer Price Index, but they're actually below historical highs.

Southwest and United Airlines Pilots Are Next

Airlines have very little negotiating power when it comes to pilots. You can't fly a plane without pilots and the overall shortage of qualified people to fill those roles means that, within reason, United (UAL) - Get Free Report and Southwest Airlines  (LUV) - Get Free Report, both of which are negotiating new deals with their pilot unions, more or less have to equal (or improve on) the Delta deal.

The actual specifics don't matter much to consumers, but the takeaway is that the cost of hiring pilots is about to go up in a very meaningful way at both United and Southwest. That will create a situation where all major U.S. airlines have a higher cost basis going forward.

Lower fuel prices could offset that somewhat, but raises are not going to be unique to pilots. Southwest also has to make a deal with its flight attendants and, although they don't have the same leverage as the pilots, they have taken a hard line.   

The union, which represents Southwest’s 18,000 flight attendants, has been working without a contract for four years. It shared a statement on its Facebook page detailing its position Feb. 20.

"TWU Local 556 believes strongly in making this airline successful and is working to ensure this company we love isn’t run into the ground by leadership more concerned about shareholders than about workers and customers. Management’s methodology of choosing profits at the expense of the operation and its workforce has to change, because the flying public is also tired of the empty apologies that flight attendants have endured for years."

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