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.
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:firstname.lastname@example.org
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: email@example.com
Angewandte Chemie International Edition, Postfach 101161, 69451 Weinheim, Germany.
Dr. Wenfu Zheng | GDCh
Researchers invent tiny, light-powered wires to modulate brain's electrical signals
21.02.2018 | University of Chicago
The “Holy Grail” of peptide chemistry: Making peptide active agents available orally
21.02.2018 | Technische Universität München
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Life Sciences
21.02.2018 | Life Sciences
21.02.2018 | Materials Sciences