Nav: Home

Multifunctional platform for the delivery of gene therapeutics

January 22, 2018

Gene editing is one of the hottest topics in cancer research. A Chinese research team has now developed a gold-nanoparticle-based multifunctional vehicle to transport the "gene scissors" to the tumor cell genome. As the authors report in the journal Angewandte Chemie, their nonviral transport and release platform of gene-editing systems has the additional advantage of combining hyperthermal cancer therapy with genetic modification.

Since its discovery in 2002, the bacterial antiviral defense strategy CRISPR-Cas9 has emerged as one of the most popular genome engineering approaches with wide applications in the fields of molecular biology and biomedicine. Using the CRISPR-Cas9 system, a target gene can be edited, knocked out, or inserted in eukaryotic cells in a relatively simple and convenient manner. However, one of its weak points is its sheer size, which demands the use of specific nonviral vehicles to deliver the large plasmid to the nucleus. Combining established lipid formulations with gold nanoparticles, Wenfu Zheng and his colleagues from the National Center for NanoScience and Technology, Beijing, China, in cooperation with medical scientists in Japan and China, have found and tested a multifunctional tool based on simple components that effectively delivers and releases the CRISPR-Cas9 system into tumors. Laser irradiation was used to disassemble the lipid-nanogold vehicle after its entry in the tumor cells and enable the CRISPR-Cas9 gene editing. The knockout of the targeted gene then led to apoptosis and tumor growth inhibition.

Gold nanoparticles are especially attractive carriers for various biological molecules because of their easy modification, stability, and light-irradiation response. To convert them into a versatile biological transport and delivery vehicle, the scientists first attached Tat peptides--which facilitate the crossing of the cell nucleus membrane--to gold nanoparticles. Then, the CRISPR-Cas9 plasmid containing the RNA targeting the Plk-1 gene--the knockout of which would severely impair tumor cell function--was attached to the Tat peptides through electrostatic interactions so that they would release their load right after entering the nucleus. Finally, the nanoparticular system was coated with a formulation of lipids to improve cellular uptake.

To test the system, cells and tumor-bearing mice were both administrated with the CRISPR-Cas9-plasmid-carrying nanogold vehicle, and the release of the gene-editing machine was triggered by a laser. "In this study, light irradiation caused the release of the Tat peptide from the gold nanoparticles in a time- and laser-intensity-dependent manner," the authors explained. Other approaches are also possible as they pointed out: as the gold nanoparticles heat up upon irradiation, they could serve as thermotherapeutic agents themselves. In summary, this relatively simple design entailing gold nanoparticles, peptides, and lipids assembled into a sophisticated multifunctional carrier/release system could serve as a multifunctional delivery platform for various aspects of gene therapy.
-end-
About the Author

Dr. Wenfu Zheng is an Associate Professor in Nanomedicine at the National Center for NanoScience and Technology, Beijing, China. His research interests span nanomaterials for drug delivery, organs-on-a-chip, and tissue engineering.

mailto:zhengwf@nanoctr.cn

Wiley

Related Gold Nanoparticles Articles:

A potential breakthrough in obesity medicine with the help of gold nanoparticles
A team of researchers in Korea believes to have discovered a synthetic gold-based compound which may help patients with obesity.
Peppered with gold
Terahertz waves are becoming more important in science and technology.
Gold nanoparticles uncover amyloid fibrils
EPFL scientists have developed powerful tools to unmask the diversity of amyloid fibrils, which are associated with Alzheimer's disease and other neurodegenerative disorders.
Gold nanoparticles detect signals from cancer cells
A novel blood test that uses gold nanoparticles to detect cancer has also been shown to identify signals released by cancer cells.
What happens to gold nanoparticles in cells?
Gold nanoparticles, which are supposed to be stable in biological environments, can be degraded inside cells.
Gold nanoparticles shown to be safe and effective treatment for prostate cancer
Bio-compatible gold nanoparticles designed to convert near-infrared light to heat have been shown to safely and effectively ablate low- to intermediate-grade tumors within the prostate, according to a study conducted at the Icahn School of Medicine and published in the journal Proceedings of the National Academy of Sciences.
Actively swimming gold nanoparticles
Bacteria can actively move towards a nutrient source -- a phenomenon known as chemotaxis -- and they can move collectively in a process known as swarming.
Ultra-thin superlattices from gold nanoparticles for nanophotonics
The group of Prof. Dr. Matthias Karg at the Institute of Physical Chemistry at Heinrich Heine University Duesseldorf (HHU) in Germany is creating ultra-thin, highly ordered layers of spherical hydrogel beads that encapsulate gold or silver particles.
Gold recycling
'Urban mining', the recycling of precious metals from electronic gadgets, becomes ever more important, although processes that are both efficient and environmentally benign are still scarce.
All that is gold is not biochemically stable
Environmental nanoparticle researchers discover that gold isn't always the shining example of a biologically stable material that it's assumed to be.
More Gold Nanoparticles News and Gold Nanoparticles Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.