Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Multifunctional Platform for the Delivery of Gene Therapeutics

22.01.2018

Thermo-triggered release of a genome-editing machinery by modified gold nanoparticles for tumor therapy

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.

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.

Author: Wenfu Zheng, National Center for Nanoscience and Technology (China), mailto:zhengwf@nanoctr.cn

Title: Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy

Angewandte Chemie International Edition
Permalink to the original article: https://doi.org/10.1002/anie.201708689 – Please use in your news piece to make sure altmetric.com picks it up and a link to your piece is shown on the journal's website.

Copy free of charge. We would appreciate a transcript of your article or a reference to it.
The original article is available from our online pressroom at http://pressroom.angewandte.org.
Contact: Editorial office: angewandte@wiley-vch.de

Angewandte Chemie is a journal of the Gesellschaft Deutscher Chemiker (German Chemical Society, GDCh) and is published by Wiley-VCH. It is one of the prime chemistry journals in the world.

Angewandte Chemie International Edition, Postfach 101161, 69451 Weinheim, Germany.

Dr. Wenfu Zheng | GDCh
Further information:
http://www.gdch.de/

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>