Researchers at UT Southwestern recently developed nanoparticles that can break down the physical barriers surrounding tumors to reach cancer cells.
As indicated in a Phys.org report, as solid tumors grow, they surround themselves with a thick, difficult-to-penetrate wall of molecular defenses. More so, getting drugs past that barrier is notoriously a struggle.
Once the nanoparticles are inside, they release their payload, a gene-editing system that changes DNA inside the tumor, barring its growth and stimulating the immune system.
The new nanoparticles described in the study effectively prevented the growth and spread of liver and ovarian tumors in mice.
According to Daniel Siegwart, Ph.D., the study leader and Associate Professor of Biochemistry at UT South Southwestern, the system is offering a new path forward for the employment of a gene-editing tool called CRISPR-Cas9 in cancer treatment.
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While the gene-editing system provides the potential to change genes that are driving cancer growth, CRISPR-Cas9 delivery to solid tumors has been challenging.
CRISPR-Cas9 Delivery to Solid Tumors, a Long-Time Challenge
A member of the Harold C. Simmons Comprehensive Cancer Center, Dr. Siegwart, explained that even though CRISPR offers a new approach to cancer treatment, the technology has been severely impeded by the delivery payloads' low efficiency into tumors.
Recently, CRISPR-Cas9 has provided researchers with an approach to selectively editing the DNA inside the living cell. While the gene-editing system offers the potential to change genes that are driving cancer growth, CRISPR-Cas9 delivery to solid tumors has been challenging.
For more than ten years, Dr. Siegwart and his colleagues have been investigating and developing lipid nanoparticles or LNPs, tiny spheres of fatty molecules that can carry molecular cargo, including recent mRNA CPVOD-19 vaccines into the human body.
In 2020, Siegwart's team showed how to direct nanoparticles to particular tissues, which had been a struggle in limiting the field.
Short Interfering RNA
In the new work published in Nature Nanotechnology, to target cancer, the study authors started with the nanoparticles that they had already optimized to travel through the liver.
They added a small piece of RNA, also known as siRNA or short interfering RNA, that could shut off focal adhesion kinase or FAK, a gene that plays a major role in holding together a number of tumors' defenses.
According to postdoctoral research fellow Di Zhang, Ph.D., from the UTSW, and the study's first author, targeting FAK not only weakens the barricade that surrounds the tumors and makes it easier for the nanoparticles themselves to make their way into the tumor but paves the way as well, to allow immune cells in.
Inside the newly contrived nanoparticles, the study investigators encapsulated CRISPR-Cas9 machinery that could edit the gene PD-L1.
Nanoparticles Treating Tumors in Mice
As indicated in the UT Southwestern Medical Center report, many cancers are using this gene to generate high levels of PD-L1 protein, which breaks the immune system's ability to attack tumors.
Nanoparticles developed by UT Southwestern researchers can travel deep into tumors to deliver drugs and activate the immune system. Learn more: https://t.co/reUilVnLLy. @DJSiegwart @CRI_UTSW @UTSWScience
— UTSW Simmons Cancer Center (@utswcancer) June 23, 2022
In connection to this, researchers have previously presented that disrupting the PD-L1 gene in certain cancers can lift such breakers and allow a person's immune system to destroy cancer cells.
Siegward, Zhang, and their colleagues tested the new nanoparticles in four mouse ovarian and liver cancer models.
The study authors initially showed that by adding siRNA to shut off FAK, the molecules' matrix around the tumors was less stiff, not to mention easier to penetrate than normal.
They initially examined the tumor cells and discovered that many more nanoparticles had reached the cells, effectively modifying the PD-L1 gene.
Lastly, the team discovered that tumors in mice treated using nanoparticles that targeted both PD-L1 and FAK shrank to roughly one-eighth the size of tumors treated with empty nanoparticles.
Additionally, more immune cells infiltrated the tumors, and the treated mice survived roughly twice as long.
Related information about nanoparticle-based drugs against cancer is shown on the Institute of Molecular Bioscience's YouTube video below:
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