Ultrasound guides supercharged immune cells to only attack cancer

Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.

The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors. CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient’s T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface.

This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity.

CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang’s lab.

The problem with standard CAR T cells is that they are always on—they are always expressing the CAR protein, so you cannot control their activation,” explained Wu.

To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on.

We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What’s exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body.

The team’s approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that’s on top of the tumor to activate the CAR T cells. The transducer uses what’s called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied.

The research was published in the journal Nature Biomedical Engineering.

How To Intercept Coronavirus Infection

Nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce. The first data describing this new direction for fighting COVID-19 were published on June 17, 2020 in the journal Nano Letters. The “nanosponges” were developed by engineers at the University of California San Diego (UC San Diego) and tested by researchers at Boston University. The UC San Diego researchers call their nano-scale particlesnanosponges” because they soak up harmful pathogens and toxins.

In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its “viral infectivity” in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.

Instead of targeting the virus itself, these nanosponges are designed to protect the healthy cells the virus invades.

Nanosponges attacking and neutralizing the SARS-COV-2 virus

Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering.

His lab first created this biomimetic nanosponge platform more than a decade ago and has been developing it for a wide range of applications ever since. When the novel coronavirus appeared, the idea of using the nanosponge platform to fight it came to Zhang “almost immediately,” he said.

In addition to the encouraging data on neutralizing the virus in cell culture, the researchers note that nanosponges cloaked with fragments of the outer membranes of macrophages could have an added benefit: soaking up inflammatory cytokine proteins, which are implicated in some of the most dangerous aspects of COVID-19 and are driven by immune response to the infection.

Source: https://ucsdnews.ucsd.edu/

Edible Sensor To Check Whether Drugs Have Been Taken

An ingestible sensor that enables health workers to check that patients have taken their medication could revolutionise tuberculosis treatment, particularly in developing countries, researchers believe. New ways to ensure TB patients comply with their treatment are desperately needed. Patients with the most straightforward form of the deadly infectious disease have to take a cocktail of drugs over a six-month period – and if they fail to stick to the regime, they risk the disease returning in a drug-resistant form.

In the study, published in in the journal Plos Medicinepatients in California were given a standard TB drug alongside an “ediblesensor, coated with minerals.  When ingested, the sensor communicates with a patch attached to the patient’s torso that in turn sends a message to a mobile phone. The data is then automatically uploaded to a secure, centralised computer for a health worker to check.

To avoid high treatment drop-out rates it is recommended that patients take their medication under the supervision of a health worker in a procedure called directly observed therapy (DOT). But this is time consuming – requiring a health worker to visit the patient at work or home or vice versa – as well as costly and inconvenient. But this new “wireless observed therapy” (WOT) avoids the need for daily visits and enables the patient to take the drugs in private and at a time that suits them.

Some 77 patients, who were no longer infectious but still needed to finish their course of treatment, took part in the study, carried out by researchers at the University of California San Diego (UCSD). A third followed the standard DOT model of care and two thirds followed the novel treatment. The study showed that WOT had a 99.3 per cent accuracy rate in recording adherence to treatment and all those patients on the wireless therapy wanted to continue with it after the trial had ended. All finished treatment and were cured of TB.

Sara Browne, lead author of the study and associate professor of infectious diseases at the UCSD, said the ingestible sensor gave patients more autonomy.

The system allows patients to determine how they want to take their pills with minimum interference. It preserves the highest standards of privacy but it also enables the health system to focus on people who need the most support,” she said.

Source: http://grantome.com/


Contact Lens Zooms On Your Command

It is absolutely the stuff of science fiction: a contact lens that zooms on your command. But scientists at the University of California San Diego have gone ahead and made it a reality. They’ve created a contact lens, controlled by eye movements, that can zoom in if you blink twice.

How is this possible? In the simplest of terms, the scientists measured the electrooculographic signals generated when eyes make specific movements (up, down, left, right, blink, double blink) and created a soft biomimetic lens that responds directly to those electric impulses. The lens created was able to change its focal length depending on the signals generated.

Therefore the lens could literally zoom in the blink of an eye. Incredibly, the lens works regardless of whether the user can see or not. It’s not about the sight, it’s about the electricity produced by specific movements.

Why create this? Why the hell not. The researchers believe this innovation could be used in “visual prostheses, adjustable glasses, and remotely operated robotics in the future,” but I’m waiting for them to turn up on CSI Miami. Could you imagine the crimes Ice-T could solve wearing these things?

Source: https://www.cnet.com/

Plant Viruses Used to Ward Off Pests

Imagine a technology that could target pesticides to treat specific spots deep within the soil, making them more effective at controlling infestations while limiting their toxicity to the environment.

Researchers at the University of California San Diego and Case Western Reserve University have taken a step toward that goal. They discovered that a biological nanoparticle—a plant virus—is capable of delivering pesticide molecules deeper below the ground, to places that are normally beyond their reach.

The work could help farmers better manage difficult pests, like parasitic nematodes that wreak havoc on plant roots deep in the soil, with less pesticide. The work is published May 20 in the journal Nature Nanotechnology.

It sounds counterintuitive that we can use a plant virus to treat plant health,” said Nicole Steinmetz, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering and senior author of the study. “This is an emerging field of research in nanotechnology showing that we can use plant viruses as pesticide delivery systems. It’s similar to how we’re using nanoparticles in medicine to target drugs towards sites of disease and reduce their side effects in patients.

Pesticides are very sticky molecules when applied in the field, Steinmetz explained. They bind strongly to organic matter in the soil, making it difficult to get enough to penetrate deep down into the root level where pests like nematodes reside and cause damage. To compensate, farmers end up applying large amounts of pesticides, which cause harmful residues to build up in the soil and leach into groundwater.

Steinmetz and her team are working to address this problem. In a new study, they discovered that a particular plant virus, Tobacco mild green mosaic virus, can transport small amounts of pesticide deep through the soil with ease.

Source: https://ucsdnews.ucsd.edu/

Nanorobots Clear Bacteria From Blood

Engineers at the University of California San Diego have developed tiny ultrasound-powered robots that can swim through blood, removing harmful bacteria along with the toxins they produce. These proof-of-concept nanorobots could one day offer a safe and efficient way to detoxify and decontaminate biological fluids.

Researchers built the nanorobots by coating gold nanowires with a hybrid of platelet and red blood cell membranes. This hybrid cell membrane coating allows the nanorobots to perform the tasks of two different cells at once—platelets, which bind pathogens like MRSA bacteria (an antibiotic-resistant strain of Staphylococcus aureus), and red blood cells, which absorb and neutralize the toxins produced by these bacteria. The gold body of the nanorobots responds to ultrasound, which gives them the ability to swim around rapidly without chemical fuel. This mobility helps the nanorobots efficiently mix with their targets (bacteria and toxins) in blood and speed up detoxification.

The work, published May 30 in Science Robotics, combines technologies pioneered by Joseph Wang and Liangfang Zhang, professors in the Department of NanoEngineering at the UC San Diego Jacobs School of Engineering. Wang’s team developed the ultrasound-powered nanorobots, and Zhang’s team invented the technology to coat nanoparticles in natural cell membranes.

SEM image of a MRSA bacterium attached to a hybrid cell membrane coated nanorobot

By integrating natural cell coatings onto synthetic nanomachines, we can impart new capabilities on tiny robots such as removal of pathogens and toxins from the body and from other matrices,” said Wang. “This is a proof-of-concept platform for diverse therapeutic and biodetoxification applications.”

The idea is to create multifunctional nanorobots that can perform as many different tasks at once,” adds co-first author Berta Esteban-Fernández de Ávila, a postdoctoral scholar in Wang’s research group at UC San Diego. “Combining platelet and red blood cell membranes into each nanorobot coating is synergistic—platelets target bacteria, while red blood cells target and neutralize the toxins those bacteria produce.

Source: http://jacobsschool.ucsd.edu/