cancer (2)



Cancer cells are one of the main targets for expanded mRNA-LNP use. Credit: Iliescu Catalin / Alamy

Topics: Biology, Biotechnology, Cancer, COVID-19, Nanotechnology

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Lipid nanoparticles (LNPs) transport small molecules into the body. The most well-known LNP cargo is mRNA, the key constituent of some of the early vaccines against COVID-19. But that is just one application: LNPs can carry many different types of payload and have applications beyond vaccines.

Barbara Mui has been working on LNPs (and their predecessors, liposomes) since she was a Ph.D. student in Pieter Cullis’s group in the 1990s. “In those days, LNPs encapsulated anti-cancer drugs,” says Mui, who is currently a senior scientist at Acuitas. This company developed the LNPs used in the Pfizer-BioNTech mRNA vaccine against SARS-CoV-2. She says it soon became clear that LNPs worked even better as carriers of polynucleotides. “The first one that worked really well was encapsulating small RNAs,” Mui recalls.

But it was mRNA where LNPs proved most effective, primarily because LNPs are comprised of positively charged lipid nanoparticles that encapsulate negatively charged mRNA. Once in the body, LNPs enter cells via endocytosis into endosomes and are released into the cytoplasm. “Without the specially designed chemistry, the LNP and mRNA would be degraded in the endosome,” says Kathryn Whitehead, professor in the departments of chemical engineering and biomedical engineering at Carnegie Mellon University.

LNPs are an ideal delivery system for mRNA. “COVID accelerated the acceptance of LNPs, and people are more interested in them,” says Mui. LNP-mRNA vaccines for other infectious diseases, such as HIV or malaria, or for non-communicable diseases, such as cancer, could be next. And the potential doesn’t end with mRNA; there is even more scope to adapt LNPs to carry different types of cargo. But to realize these potential benefits, researchers first need to overcome challenges and decrease toxicity, increase their ability to escape from the endosomes, increase their thermostability, and work out how to effectively target LNPs to organs across the body.

Another potential application for LNPs is immunotherapy. Genetically modifying lymphocytes such as T cells or NK cells with chimeric antibody receptors (CARs) has proven useful in blood cancers. Often this process involves extracting lymphocytes from the blood of the person receiving the treatment, editing the cells in culture to express CARs, and then reintroducing them into the blood. However, LNPs could make it possible to express the desired CAR in vivo by shuttling CAR mRNA to the target lymphocytes. Mui has been involved in vivo studies showing this process works in mouse T cells (Rurik, J.G. et al. Science 375, 91-96, 2022). And Vita Golubovskaya, VP of research and development at ProMab Biotechnologies, presented preliminary data (available here) at the CAR-TCR Summit in September 2022 regarding LNPs that direct CAR-mRNA to NK cells, which can then kill target cells. “The RNA-LNP is a very exciting and novel technology that can be used for delivering CAR and bi-specific antibodies against cancer,” she says.

Beyond COVID vaccines: what’s next for lipid nanoparticles? Nature Portfolio

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Microbots and Chemo..


Credit: Gao Wang

Topics: Biology, Cancer, Chemotherapy, Robotics

Chemotherapy disrupts cancer cells’ ability to reproduce by frustrating cell division and damaging the cells’ DNA. In response to the pharmaceutical onslaught, cancer cells acquire mutations that reduce the therapy’s effectiveness. Compounding the challenge of fighting cancer: Under chemical and other stresses, mutation rates increase.

A team led by Princeton University’s Robert Austin and Chongqing University’s Liyu Liu has developed a novel approach to study—and potentially thwart—cancer cells’ adaptation to chemotherapy. Their cancer cell analogs are wheeled, cylindrical robots about 65 mm in diameter and 60 mm in height (see photo above). Fifty of the robots roll independently of each other over a square table, whose 4.2 × 4.2 m2 surface is covered by 2.7 million LEDs (see photo below). Light from the LEDs serves as the robots’ food. Once a robot has “eaten” the light beneath it, the corresponding LEDs are dimmed until they recover a fixed time later.

The bottom surface of each robot is equipped with four semiconductor-based sensors that can detect the intensities and spatial gradients of the three colors of light emitted by the light table: red, green, and blue (RGB). Each robot’s six-byte genome analog determines how sensitive it is to the three colors. The sensitivity, in turn, determines how readily the robot moves in response to the colors’ intensities and spatial gradients.

Evolving robots could optimize chemotherapy, Charles Day, Physics Today

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