Viruses are able to redirect the functioning of cells in order to infect them. Inspired by their mode of action, scientists from the CNRS and Université de Strasbourg have designed a “chemical virus” that can cross the double lipid layer that surrounds cells, and then disintegrate in the intracellular medium in order to release active compounds.
To achieve this, the team used two polymers they had designed, which notably can self-assemble or dissociate, depending on the conditions. This work, the result of collaborative efforts by chemists, biologists and biophysicists, is published in the 1st September issue of Angewandte Chemie International Edition.
Biotechnological advances have offered access to a wealth of compounds with therapeutic potential. Many of these compounds are only active inside human cells but remain unusable because the lipid membrane surrounding these cells is a barrier they cannot cross. The challenge is therefore to find transfer solutions that can cross this barrier.
By imitating the ability of viruses to penetrate into cells, chemists in the Laboratoire de Conception et Application de Molécules Bioactives (CNRS/Université de Strasbourg) sought to design particles capable of releasing macromolecules that are only active inside cells. To achieve this, these particles must comply with several, often contradictory, constraints. They must remain stable in the extracellular medium, they must be able to bind to the cells so that they be internalized, but they must be more fragile inside the cells so that they can release their content.
Using two polymers designed by the team, the scientists succeeded in creating a “chemical virus” that meets the conditions necessary for the direct delivery of active proteins into cells.
In practice, the first polymer (pGi-Ni2+) serves as a substrate for the proteins that bind to it. The second, recently patented polymer (?PEI), encapsulates this assembly thanks to its positive charges, which bind to the negative charges of pGi-Ni2+. The particles obtained (30-40 nanometers in diameter) are able to recognize the cell membrane and bind to it. This binding activates a cellular response: the nanoparticle is surrounded by a membrane fragment and enters the intracellular compartment, called the endosome. Although they remain stable outside the cell, the assemblies are attacked by the acidity that prevails within this new environment. Furthermore, this drop in pH allows the ?PEI to burst the endosome, releasing its content of active compounds.
Thanks to this assembly, the scientists were able to concentrate enough active proteins within the cells to achieve a notable biological effect. Thus by delivering a protein called caspase 3 into cancer cell lines, they succeeded in inducing 80% cell death1.
The in vitro results are encouraging, particularly since this “chemical virus” only becomes toxic at a dose ten times higher than that used during the study. Furthermore, preliminary results in the mouse have not revealed any excess mortality. However, elimination by the body of the two polymers remains an open question. The next stage will consist in testing this method in-depth and in vivo, in animals. In the short term, this system will serve as a research tool to vectorize2 recombinant and/or chemically modified proteins into cells. In the longer term, this work could make it possible to apply pharmaceutical proteins to intracellular targets and contribute to the development of innovative drugs.
Read more: Imitating viruses to deliver drugs to cells
The Latest on: Imitating viruses to deliver drugs to cells
via Google News
The Latest on: Imitating viruses to deliver drugs to cells
- Outsmart the scammers: Fake messages that look so real. 'Bank staff' calling you from genuine numbers to get you to transfer thousands... Here are the scammers' top ten tricks ...on October 8, 2021 at 5:49 pm
Once you open the link, you may be directed to a dodgy website which could download viruses onto your computer ... offering cheap travel deals, often imitating well-known brands.
- A.G. Merrick Garland Tells FBI To Investigate Parents Who Yell at School Officials About Critical Race Theoryon October 6, 2021 at 8:21 am
Taking note of a supposed "spike" in harassment and intimidating behavior directed at public school officials, Attorney General Merrick Garland has instructed the FBI to be on the lookout for ...
- Valued to be $2.8 Billion by 2026, ePRO, E-Patient Diaries and eCOA Slated for Robust Growth Worldwideon October 5, 2021 at 8:31 am
SAN FRANCISCO, Oct. 5, 2021 /PRNewswire/ -- A new market study published by Global Industry Analysts Inc., (GIA) the premier market research company, today released its report titled "ePRO, E ...
- CNN’s René Marsh fights for change after losing 2-year-old son to brain canceron September 28, 2021 at 3:51 am
The first step was surgery to remove Blake's tumor. Then doctors presented Marsh and her husband with a treatment plan involving chemotherapy drugs. Chemotherapy is designed to kill cancer cells and ...
- Engage Tinfoil Hat: Samsung Note 7 Battery Theoryon September 27, 2021 at 5:00 pm
It’s a computer virus that infected and took down the centrifuges ... Smartphones usually have a single cell, but there is still data there — a third conductor that can transfer data like ...
- My Anti-Vax Siblings’ Selfishness Destroyed My Chance To Mourn My Dead Brotheron September 24, 2021 at 2:00 am
We kids would huddle in a corner imitating the adults and sneak sips of wine. COVID-19 stole these complex and messy traditions from many of us over the last 19 months, and it was especially tragic ...
- Jounce Therapeutics Appoints Jigar Raythatha to its Board of Directorson September 15, 2021 at 5:02 am
“Over the course of the last several years, Jounce has established a strong position as a leader in novel immuno-oncology drug discovery ... deplete T regulatory cells in the tumor ...
- DNA nanomachineson September 10, 2021 at 12:51 am
intelligent drug delivery or programmable chemical synthesis. Biological molecular motors that carry cargoes within cells have inspired the construction of rudimentary DNA walkers that run along ...
- Researchers develop artificial inorganic cell-like structures to recreate functions of living cellson September 8, 2021 at 9:37 pm
Their article, published in Nature, provides a blueprint for creating "cell mimics," with potential applications ranging from drug delivery to ... can be exchanged, imitating a cell's protein ...
- CORRECTED-COVID SCIENCE-mRNA vaccines trigger backup immune response; some cancer drugs may helpon August 25, 2021 at 2:05 pm
The drugs, known as mTOR/PI3K inhibitors and antimetabolites, target the parts of cells that the virus uses to enter and make copies of itself, including a "gateway" protein on cell surfaces called ...
via Bing News