Passport application appointments scarce, leading to months-long waits

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Jon Poganski was worried he wasn't going to make it to Toronto, Canada, to help his team in a race car series. He faced the challenge of trying to get a passport, though he said the process of applying for one was the easy part. 

Finding an appointment to apply for one, on the other hand, wasn't so easy. 

Poganski couldn't find a passport acceptance center. That's because most places are completely booked with no available appointment windows.

In Northern California, some locations have no available appointments until the middle of September. 


The United States Postal Service passport acceptance facility accepts walk-ins for the service, but nearly every appointment was booked for the next 45 days. 

"Because of the surge in demand for passports, we are seeing a large volume of requests for passport appointments," a USPS spokesperson.

This leads to situations like Poganski's. Travelers may not be able to make scheduled travel due to the demand.

"It did take a little time to plan it," Poganski said, adding he had to drive more than an hour to find an acceptance facility that was able to accept his passport application.

The Sutter County clerk-recorder's office is one of the few passport acceptance facilities in Northern California that only accepts walk-ins and doesn't schedule appointments. 

"There was a time when the passport agency wasn’t accepting any applications, so we’ve got that backlog of folks wanting to get an application," Clerk-Recorder Donna Johnston said. 


Johnston said customers begin to line up early in the morning before the office even opens to make sure they can submit their passport applications. The acceptance center will then send the applications to the State Department for processing. 

"I got a co-worker to come in early, so I could be here when they opened at 7," Poganski said. Johnston said they occasionally have travelers to the office from out of state to submit applications. 


"Having travel restrictions eased up has increased the number of people coming in as well," Johnston said. 

State Department data shows a sharp decline in passports issued during the pandemic in 2020

Just under 12 million passports were issued in 2020, compared to the more than 20 million in 2019. In 2021, more than 15 million passports were issued. 

"To avoid delays and potential travel disruptions, U.S. citizens and nationals should apply as early as they can for a new passport," a State Department spokesperson said. 

Due to the lack of appointments and factoring in the processing times, it could take months to get a passport. 

The current processing time for a passport is 8-11 weeks for routine service and 5-7 weeks for expedited service. These time frames represent waits after applications arrive at a passport agency. 

Source: Passport application appointments scarce, leading to months-long waits

Woman on Malta trip has incomplete miscarriage but can't get abortion due to Maltese law

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A pregnant American woman who suffered an incomplete miscarriage while vacationing in Malta will be airlifted to Spain on Thursday for a procedure to prevent infection because Maltese law prohibits abortion under any circumstances, the woman's partner said.

Jay Weeldreyer told The Associated Press by phone from a hospital in the island nation that his partner, Andrea Prudente, is at risk of a life-threatening infection if the fetal tissue isn’t promptly removed.

Prudente, 38, experienced heavy bleeding on June 12, followed by a premature rupture of the amniotic sac and the separation of the placenta, according to Weeldreyer, 45. While the hospital is carefully monitoring her for any sign of infection, the facility cannot perform the surgery to complete the miscarriage, he said.

Malta is the only European Union member nation that outlaws abortions for any reason. Contacted by The AP, Mater Dei Hospital, where Prudente is being treated, said it wasn’t allowed to give out patient information due to privacy regulations.

"The miscarriage is 80% complete,'' Weeldreyer said. "Her waters are broken, the placenta has separated, but because of a (fetal) heartbeat," the fetus cannot be removed, he said. In separate comments to other news outlets, the couple described the placenta as being partially detached.


Mater Dei Hospital, a public facility in Malta, declined to speak about the woman's medical condition, citing privacy restrictions.

The couple from Issaquah, Washington, a town near Seattle, arrived in Malta on June 5 for a long-awaited vacation. Prudente started bleeding and was hospitalized a week later, her partner said. He indicated she was 16-weeks pregnant when the bleeding began.


Along with the worrying about the infection risk, the two fear Prudente might resume hemorrhaging during the medical evacuation flight they have arranged for Thursday evening to take them to the Spain, where she will be admitted to a hospital.


Mater Dei Hospital "has done a good job within the realm of what they are allowed to do" under Maltese law, Weeldreyer said. The woman is receiving antibiotics and being closely monitored for signs of infection, he said.

Source: Woman on Malta trip has incomplete miscarriage but can't get abortion due to Maltese law

New model helps identify mutations that drive cancer

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Cancer cells can have thousands of mutations in their DNA. However, only a handful of those actually drive the progression of cancer; the rest are just along for the ride.

Distinguishing these harmful driver mutations from the neutral passengers could help researchers identify better drug targets. To boost those efforts, an MIT-led team has built a new computer model that can rapidly scan the entire genome of cancer cells and identify mutations that occur more frequently than expected, suggesting that they are driving tumor growth. This type of prediction has been challenging because some genomic regions have an extremely high frequency of passenger mutations, drowning out the signal of actual drivers.

“We created a probabilistic, deep-learning method that allowed us to get a really accurate model of the number of passenger mutations that should exist anywhere in the genome,” says Maxwell Sherman, an MIT graduate student. “Then we can look all across the genome for regions where you have an unexpected accumulation of mutations, which suggests that those are driver mutations.”

In their new study, the researchers found additional mutations across the genome that appear to contribute to tumor growth in 5 to 10 percent of cancer patients. The findings could help doctors to identify drugs that would have greater chance of successfully treating those patients, the researchers say. Currently, at least 30 percent of cancer patients have no detectable driver mutation that can be used to guide treatment.

Sherman, MIT graduate student Adam Yaari, and former MIT research assistant Oliver Priebe are the lead authors of the study, which appears today in Nature Biotechnology. Bonnie Berger, the Simons Professor of Mathematics at MIT and head of the Computation and Biology group at the Computer Science and Artificial Intelligence Laboratory (CSAIL), is a senior author of the study, along with Po-Ru Loh, an assistant professor at Harvard Medical School and associate member of the Broad Institute of MIT and Harvard. Felix Dietlein, an associate professor at Harvard Medical School and Boston Children’s Hospital, is also an author of the paper.

A new tool

Since the human genome was sequenced two decades ago, researchers have been scouring the genome to try to find mutations that contribute to cancer by causing cells to grow uncontrollably or evade the immune system. This has successfully yielded targets such as epidermal growth factor receptor (EGFR), which is commonly mutated in lung tumors, and BRAF, a common driver of melanoma. Both of these mutations can now be targeted by specific drugs.

While those targets have proven useful, protein-coding genes make up only about 2 percent of the genome. The other 98 percent also contains mutations that can occur in cancer cells, but it has been much more difficult to figure out if any of those mutations contribute to cancer development.

“There has really been a lack of computational tools that allow us to search for these driver mutations outside of protein-coding regions,” Berger says. “That's what we were trying to do here: design a computational method to let us look at not only the 2 percent of the genome that codes for proteins, but 100 percent of it.”

To do that, the researchers trained a type of computational model known as a deep neural network to search cancer genomes for mutations that occur more frequently than expected. As a first step, they trained the model on genomic data from 37 different types of cancer, which allowed the model to determine the background mutation rates for each of those types.

“The really nice thing about our model is that you train it once for a given cancer type, and it learns the mutation rate everywhere across the genome simultaneously for that particular type of cancer,” Sherman says. “Then you can query the mutations that you see in a patient cohort against the number of mutations you should expect to see.”

The data used to train the models came from the Roadmap Epigenomics Project and an international collection of data called the Pan-Cancer Analysis of Whole Genomes (PCAWG). The model’s analysis of this data gave the researchers a map of the expected passenger mutation rate across the genome, such that the expected rate in any set of regions (down to the single base pair) can be compared to the observed mutation count anywhere across the genome.

Changing the landscape

Using this model, the MIT team was able to add to the known landscape of mutations that can drive cancer. Currently, when cancer patients’ tumors are screened for cancer-causing mutations, a known driver will turn up about two-thirds of the time. The new results of the MIT study offer possible driver mutations for an additional 5 to 10 percent of the pool of patients.

One type of noncoding mutation the researchers focused on is called “cryptic splice mutations.” Most genes consist of sequences of exons, which encode protein-building instructions, and introns, which are spacer elements that usually get trimmed out of messenger RNA before it is translated into protein. Cryptic splice mutations are found in introns, where they can confuse the cellular machinery that splices them out. This results in introns being included when they shouldn’t be.

Using their model, the researchers found that many cryptic splice mutations appear to disrupt tumor suppressor genes. When these mutations are present, the tumor suppressors are spliced incorrectly and stop working, and the cell loses one of its defenses against cancer. The number of cryptic splice sites that the researchers found in this study accounts for about 5 percent of the driver mutations found in tumor suppressor genes.

Targeting these mutations could offer a new way to potentially treat those patients, the researchers say. One possible approach that is still in development uses short strands of RNA called antisense oligonucleotides (ASOs) to patch over a mutated piece of DNA with the correct sequence.

“If you could make the mutation disappear in a way, then you solve the problem. Those tumor suppressor genes could keep operating and perhaps combat the cancer,” Yaari says. “The ASO technology is actively being developed, and this could be a very good application for it.”

Another region where the researchers found a high concentration of noncoding driver mutations is in the untranslated regions of some tumor suppressor genes. The tumor suppressor gene TP53, which is defective in many types of cancer, was already known to accumulate many deletions in these sequences, known as 5’ untranslated regions. The MIT team found the same pattern in a tumor suppressor called ELF3.

The researchers also used their model to investigate whether common mutations that were already known might also be driving different types of cancers. As one example, the researchers found that BRAF, previously linked to melanoma, also contributes to cancer progression in smaller percentages of other types of cancers, including pancreatic, liver, and gastroesophageal.

“That says that there’s actually a lot of overlap between the landscape of common drivers and the landscape of rare drivers. That provides opportunity for therapeutic repurposing,” Sherman says. “These results could help guide the clinical trials that we should be setting up to expand these drugs from just being approved in one cancer, to being approved in many cancers and being able to help more patients.”

The research was funded, in part, by the National Institutes of Health and the National Cancer Institute.

Source: New model helps identify mutations that drive cancer

QS ranks MIT the world’s No. 1 university for 2022-23

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MIT has again been named the world’s top university by the QS World University Rankings, which were announced today. This is the 11th year in a row MIT has received this distinction.

The full 2022 edition of the rankings — published by Quacquarelli Symonds, an organization specializing in education and study abroad — can be found at The QS rankings were based on academic reputation, employer reputation, citations per faculty, student-to-faculty ratio, proportion of international faculty, and proportion of international students.

MIT was also ranked the world’s top university in 12 of the subject areas ranked by QS, as announced in April of this year.

The Institute received a No. 1 ranking in the following QS subject areas: Architecture/Built Environment; Chemistry; Computer Science and Information Systems; Chemical Engineering; Civil and Structural Engineering; Electrical and Electronic Engineering; Materials Science; Mechanical, Aeronautical, and Manufacturing Engineering; Linguistics; Mathematics; Physics and Astronomy; and Statistics and Operational Research.

MIT also placed second in two subject areas: Biological Sciences; and Economics and Econometrics.

Source: QS ranks MIT the world’s No. 1 university for 2022-23

Mobilizing across borders to address global challenges

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For the most creative minds to work together to solve the world’s greatest challenges, it is essential for global collaboration to be unencumbered by distance. The MIT International Science and Technology Initiatives (MISTI) Global Seed Funds (GSF) program enables participating faculty teams to collaborate across borders with international partners to develop and launch joint research projects.

MISTI GSF is comprised of a general fund, open to any country, and a number of country-, region-, or university-specific funds. The resulting partnerships allow access to environmental resources, cutting-edge laboratory equipment, and perspectives not available on the Cambridge, Massachusetts, campus. GSF has made global research partnerships possible since 2008.

“[Our] collaboration was extremely fruitful,” says 2018 Israel fund recipient and MIT professor of architectural history and theory Mark Jarzombek. “The insights and knowledge brought to architecture students, both from local experts and particularly from the field of archeology, allowed them to approach the project from a unique perspective and disciplinary lens.”

Ellen Roche, the W.M. Keck Career Development Professor in Biomedical Engineering at MIT, had a similar experience with her 2018 collaboration with Spain: “Sending prototypes from one country to another and communicating transfer of manufacturing was sometimes challenging. However, working with Jose and his team was invaluable for their particle image velocimetry expertise.”

The 27 funds that comprise the MISTI GSF 2021-22 cycle awarded over $1.6 million to 75 projects from 20 departments across all of the schools in the Institute. This year's awards bring the total amount to $22.6 million funding 1,113 projects over the 14-year life of the program. This year, new funds helped MIT faculty collaborate further into Eastern Europe; funds in the Czech Republic, Poland, and Slovakia were met with a large number of excited applicants. Over 70 percent of all MIT faculty members have submitted a GSF proposal, with many receiving multiple awards.

“We have applied for [another] Global Seed Fund to facilitate a similar project in Berlin,” shares Jarzombek. “We hope to expand the breadth and goals of the method we developed and to continue to examine and explore its pedagogical and scholarly implications for the field of architectural history and pedagogy in various sites across the globe.”

Faculty seed funds also provide meaningful educational opportunities for students. The majority of GSF teams include students, contributing to both the Institute’s educational mission and commitment to encouraging intercultural learning.

“It was my intuition when I [applied for a] GSF project that we need to engage students,” says MIT associate professor of metallurgy Antoine Allanore of his 2017 U.K. collaboration. “It is the way to make this a meaningful experience for all.”

On top of building their expertise, students are often able to contribute to the faculty member’s groundbreaking research at a high level. “Two of [our] students were extremely involved and helpful in the fieldwork and study of the site,” says Jarzombek. “We could not have achieved what we have without them.”

Helping unite top academics from around the globe to address the most pressing critical issues, GSF fosters lasting connections between MIT and other leading research institutions. Most GSF projects have often culminated in published research and many have leveraged their early results to obtain additional research funding.

“We are submitting a paper this year on the work on single ventricle disease, and we have also recently started a collaboration with another group in Barcelona,” says Roche. The collaborators also secured additional funding from La Caixa Bank and have submitted an additional application to the National Science Foundation.

“[Our] highly successful seed grant resulted in a publication in the premier conference in bioinformatics and in an awarded BSF [United States-Israel Binational Science Foundation] grant proposal,” says Bonnie Berger, the Simons Professor of Mathematics at MIT and a 2020 Israel fund recipient. “We thank MISTI for funding us with the seed grant, which allowed us to achieve these goals.”

The next call for proposals will be in mid-September. “Now that global travel has nearly fully reopened, we expect even more applications next year,” says MISTI Assistant Director Alicia Raun. “We can’t wait to see what innovative ideas our faculty bring to us next.”

MISTI is MIT’s hub for global experiences, providing immersive international programs that bring MIT’s one-of-a-kind learning model to life in countries around the world. MISTI empowers students and faculty to build cultural connections, make an impact in the world, and gain valuable perspectives that inform their education, career, and worldview.

Source: Mobilizing across borders to address global challenges

French prehistoric cave in Marseille to open new exhibit

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A permanent virtual exhibit of one of France’s most famous prehistoric sites, the undersea Cosquer Cave, is set to open its doors as concerns grow that it could be completely inundated as a result of rising tides driven by climate change.

As of Saturday, visitors to the port city of Marseille will be able to see the Cosquer Mediterranee, a replica of the over 30,000-year old site. The visual and audio "experience" features copies of the prehistoric paintings that made the cave internationally famous.


The Cosquer Cave was discovered in 1985 by diver Henri Cosquer, in deep waters off the Marseille coastline.


Years in the making, the exhibit offers the chance to the public to discover the cave of which only 20% currently remains dry and accessible. Officials say the cave's remaining dry areas are under threat of being flooded because of the effects of climate change.

Source: French prehistoric cave in Marseille to open new exhibit

Most Frequently Asked Questions About Affiliate Marketing

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Most Frequently Asked Questions About Affiliate Marketing

There are lots of questions floating around about how affiliate marketing works, what to do and what not to do when it comes to setting up a business. With so much uncertainty surrounding both personal and business aspects of affiliate marketing. In this post, we will answer the most frequently asked question about affiliate marketing

1. What is affiliate marketing?

 Affiliate marketing is a way to make money by promoting the products and services of other people and companies. You don't need to create your product or service, just promote existing ones. That's why it's so easy to get started with affiliate marketing. You can even get started with no budget at all!

2. What is an affiliate program?

 An affiliate program is a package of information you create for your product, which is then made available to potential publishers. The program will typically include details about the product and its retail value, commission levels, and promotional materials. Many affiliate programs are managed via an affiliate network like ShareASale, which acts as a platform to connect publishers and advertisers, but it is also possible to offer your program directly.

3. What is an affiliate network and how do affiliate networks make money? 

 Affiliate networks connect publishers to advertisers.  Affiliate networks make money by charging fees to the merchants who advertise with them; these merchants are known as advertisers. The percentage of each sale that the advertiser pays is negotiated between the merchant and the affiliate network.

4. What's the difference between affiliate marketing and dropshipping?

 Dropshipping is a method of selling that allows you to run an online store without having to stock products. You advertise the products as if you owned them, but when someone makes an order, you create a duplicate order with the distributor at a reduced price. The distributor takes care of the post and packaging on your behalf. As affiliate marketing is based on referrals and this type of drop shipping requires no investment in inventory when a customer buys through the affiliate link, no money exchanges hands.

 5. Can affiliate marketing and performance marketing be considered the same thing?

 Performance marketing is a method of marketing that pays for performance, like when a sale is made or an ad is clicked This can include methods like PPC (pay-per-click) or display advertising. Affiliate marketing is one form of performance marketing where commissions are paid out to affiliates on a performance basis when they click on their affiliate link and make a purchase or action.

 6. Is it possible to promote affiliate offers on mobile devices?

 Smartphones are essentially miniature computers, so publishers can display the same websites and offers that are available on a PC. But mobiles also offer specific tools not available on computers, and these can be used to good effect for publishers. Publishers can optimize their ads for mobile users by making them easy to access by this audience. Publishers can also make good use of text and instant messaging to promote their offers. As the mobile market is predicted to make up 80% of traffic in the future, publishers who do not promote on mobile devices are missing out on a big opportunity.

7. Where do I find qualified publishers?

 The best way to find affiliate publishers is on reputable networks like ShareASale Cj(Commission Junction), Awin, and Impact radius. These networks have a strict application process and compliance checks, which means that all affiliates are trustworthy.

8. What is an affiliate disclosure statement?

 An affiliate disclosure statement discloses to the reader that there may be affiliate links on a website, for which a commission may be paid to the publisher if visitors follow these links and make purchases.

 9. Does social media activity play a significant role in affiliate marketing?

 Publishers promote their programs through a variety of means, including blogs, websites, email marketing, and pay-per-click ads. Social media has a huge interactive audience, making this platform a good source of potential traffic.

10. What is a super affiliate?

 A super affiliate is an affiliate partner who consistently drives a large majority of sales from any program they promote, compared to other affiliate partners involved in that program.  Affiliates make a lot of money from affiliate marketing Pat Flynn earned more than $50000 in 2013 from affiliate marketing.

11. How do we track publisher sales activity?

 Publishers can be identified by their publisher ID, which is used in tracking cookies to determine which publishers generate sales. The activity is then viewed within a network's dashboard.

 12. Could we set up an affiliate program in multiple countries?

 Because the Internet is so widespread, affiliate programs can be promoted in any country. Affiliate strategies that are set internationally need to be tailored to the language of the targeted country.

13. How can affiliate marketing help my business?

Affiliate marketing can help you grow your business in the following ways:

  •  It allows you to save time and money on marketing, which frees you up to focus on other aspects of your business.
  •  You get access to friendly marketers who are eager to help you succeed. 
  • It also helps you to promote your products by sharing links and banners with a new audience.
  •  It offers high ROI(Return on investment) and is cost-effective.

 14. How do I find quality publishers?

 One of the best ways to work with qualified affiliates is to hire an affiliate marketing agency that works with all the networks. Affiliates are carefully selected and go through a rigorous application process to be included in the network.

15. How Can we Promote Affiliate Links?

 Affiliate marketing is generally associated with websites, but there are other ways to promote your affiliate links, including:

  • A website or blog
  • Through email marketing and newsletter
  • Social media, like Facebook, Instagram, or Twitter.
  •  Leave a comment on blogs or forums.
  • Write an e-book or other digital product.
  • Youtube

 16. Do you have to pay to sign up for an affiliate program?

 To build your affiliate marketing business, you don't have to invest money in the beginning. You can sign up for free with any affiliate network and start promoting their brands right away.

17. What is a commission rate?

 Commission rates are typically based on a percentage of the total sale and in some cases can also be a flat fee for each transaction. The rates are set by the merchant.

Who manages your affiliate program?

 Some merchants run their affiliate programs internally, while others choose to contract out management to a network or an external agency.

18. What is a cookie?

 Cookies are small pieces of data that work with web browsers to store information such as user preferences, login or registration data, and shopping cart contents. When someone clicks on your affiliate link, a cookie is placed on the user's computer or mobile device. That cookie is used to remember the link or ad that the visitor clicked on. Even if the user leaves your site and comes back a week later to make a purchase, you will still get credit for the sale and receive a commission it depends on the site cookies duration

19. How long do cookies last?

 The merchant determines the duration of a cookie, also known as its “cookie life.” The most common length for an affiliate program is 30 days. If someone clicks on your affiliate link, you’ll be paid a commission if they purchase within 30 days of the click.

Final Saying

Most new affiliates are eager to begin their affiliate marketing business. Unfortunately, there is a lot of bad information out there that can lead inexperienced affiliates astray. Hopefully, the answer to your question will provide clarity on how affiliate marketing works and the pitfalls you can avoid. Most importantly, keep in mind that success in affiliate marketing takes some time. Don't be discouraged if you're not immediately making sales or earning money. It takes most new affiliates months to make a full-time income.

Source: Most Frequently Asked Questions About Affiliate Marketing

Engineers develop nanoparticles that cross the blood-brain barrier

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There are currently few good treatment options for glioblastoma, an aggressive type of brain cancer with a high fatality rate. One reason that the disease is so difficult to treat is that most chemotherapy drugs can’t penetrate the blood vessels that surround the brain.

A team of MIT researchers is now developing drug-carrying nanoparticles that appear to get into the brain more efficiently than drugs given on their own. Using a human tissue model they designed, which accurately replicates the blood-brain barrier, the researchers showed that the particles could get into tumors and kill glioblastoma cells.

Many potential glioblastoma treatments have shown success in animal models but then ended up failing in clinical trials. This suggests that a better kind of modeling is needed, says Joelle Straehla, the Charles W. and Jennifer C. Johnson Clinical Investigator at MIT’s Koch Institute for Integrative Cancer Research, an instructor at Harvard Medical School, and a pediatric oncologist at Dana-Farber Cancer Institute.

“We are hoping that by testing these nanoparticles in a much more realistic model, we can cut out a lot of the time and energy that’s wasted trying things in the clinic that don’t work,” she says. “Unfortunately, for this type of brain tumor, there have been hundreds of trials that have had negative results.”

Straehla and Cynthia Hajal SM ’18, PhD ’21, a postdoc at Dana-Farber, are the lead authors of the study, which appears this week in the Proceedings of the National Academy of Sciences. Paula Hammond, an MIT Institute Professor, head of the Department of Chemical Engineering, and a member of the Koch Institute; and Roger Kamm, the Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, are the senior authors of the paper.

Modeling the blood-brain barrier

Several years ago, Kamm’s lab began working on a microfluidic model of the brain and the blood vessels that make up the blood-brain barrier.

Because the brain is such a vital organ, the blood vessels surrounding the brain are much more restrictive than other blood vessels in the body, to keep out potentially harmful molecules.

To mimic that structure in a tissue model, the researchers grew patient-derived glioblastoma cells in a microfluidic device. Then, they used human endothelial cells to grow blood vessels in tiny tubes surrounding the sphere of tumor cells. The model also includes pericytes and astrocytes, two cell types that are involved in transporting molecules across the blood-brain barrier.

While Hajal was working on this model as a graduate student in Kamm’s lab, she got connected with Straehla, then a postdoc in Hammond’s lab, who was interested in finding new ways to model nanoparticle drug delivery to the brain. Getting drugs across the blood-brain barrier is critical for improving treatment for glioblastoma, which is usually treated with a combination of surgery, radiation, and the oral chemotherapy temozolomide. The five-year survival rate for the disease is less than 10 percent.

Hammond’s lab pioneered a technique called layer-by-layer assembly, which they can use to create surface-functionalized nanoparticles that carry drugs in their core. The particles that the researchers developed for this study are coated with a peptide called AP2, which has been shown in previous work to help nanoparticles get through the blood brain barrier. However, without accurate models, it was difficult to study how the peptides helped with transport across blood vessels and into tumor cells.

When the researchers delivered these nanoparticles to tissue models of both glioblastoma and healthy brain tissue, they found that the particles coated with the AP2 peptide were much better at penetrating the vessels surrounding the tumors. They also showed that the transport occurred due to binding a receptor called LRP1, which is more abundant near tumors than in normal brain vessels.

The researchers then filled the particles with cisplatin, a commonly used chemotherapy drug. When these particles were coated with the targeting peptide, they were able to effectively kill glioblastoma tumor cells in the tissue model. However, particles that didn’t have the peptides ended up damaging the healthy blood vessels instead of targeting the tumors.

“We saw increased cell death in tumors that were treated with the peptide-coated nanoparticle compared to the bare nanoparticles or free drug. Those coated particles showed more specificity of killing the tumor, versus killing everything in a nonspecific way,” Hajal says.

More effective particles

The researchers then tried delivering the nanoparticles to mice, using a specialized surgical microscope to track the nanoparticles moving through the brain. They found that the particles’ ability to cross the blood-brain barrier was very similar to what they had seen in their human tissue model.

They also showed that coated nanoparticles carrying cisplatin could slow down tumor growth in mice, but the effect wasn’t as strong as what they saw in the tissue model. This might be because the tumors were in a more advanced stage, the researchers say. They now hope to test other drugs, carried by a variety of nanoparticles, to see which might have the greatest effect. They also plan to use their approach to model other types of brain tumors.

“This is a model that we could use to design more effective nanoparticles,” Straehla says. “We've only tested one type of brain tumor, but we really want to expand and test this with a lot of others, especially rare tumors that are difficult to study because there may not be as many samples available.”

The researchers described the method they used to create the brain tissue model in a recent Nature Protocols paper, so that other labs can also use it.

The research was funded, in part, by a Cooperative Agreement Award from the National Cancer Institute, a Horizon Award from the Department of Defense Peer Reviewed Cancer Research Program, a Cancer Research UK Brain Tumour Award, a Ludwig Center for Molecular Oncology Graduate Fellowship, the Rally Foundation for Childhood Cancer Research/The Truth 365, the Helen Gurley Brown Presidential Initiative, and the Koch Institute Support (core) Grant from the National Cancer Institute.

Source: Engineers develop nanoparticles that cross the blood-brain barrier