Neurons differentiated with artificial cells shown through a fluorescence microscope at 20X magnification. PHOTO BY SUPPLIED /University of Alberta

Smart pharmaceuticals could treat disease autonomously at a cellular level.

Researchers from the University of Alberta describe a novel artificial cell that can communicate with other cells within the body, in a step towards smart pharmaceuticals of the future.

Smart pharmaceuticals are synthetic entities that could one day monitor, target, and treat disease autonomously while in the host body. These artificial cells are in effect biocomputers that in the future could detect and respond to cancer, deliver antibiotics upon the detection of a bacterial infection, or even release dopamine to treat neurological disorders as and when needed. However, thus far artificial cells capable of being programmed or interacting with native eukaryotic cells have yet to be tested in living systems.

Artificial cells that can influence native cells

Now, a study from researchers led by the University of Alberta engineers artificial smart cells capable of communicating with the living cells around them to influence their behavior. The team states the synthetic cells work by detecting changes in their environment within the body. In response, the smart pharmaceuticals then synthesize and release a protein signal that controls biological cells under physiological conditions. The opensource study is published in the journal Science Advances.

Previous studies predict artificial cells with the ability to assimilate with living systems may help uncover cell-to-cell interactions on the nanoscale. This is expected to lead to drug delivery on a single-cell level. These smart pharmaceuticals could then monitor the host in realtime in a way that does not flood the entire organism with drug molecules. Subsequently, this would greatly lessen the risk of adverse events or the occurrence of drug resistance.

To date, most attempts at building artificial cells focus on providing biomimetic properties under laboratory conditions in the absence of other living cells. Accordingly, the synthetic cells are programmed to act as their native counterparts, however, they have not been tested in complex biological systems where their natural counterparts are found. To this end, a handful of laboratories have begun to assemble more diverse ecosystems consisting solely of artificial cells, or synthetic cells mixed with natural living cells. Nevertheless, the whole physiological ecosystem is yet to be simulated.

The current study reports the construction of smart pharmaceuticals that chemically communicate with mammalian cells under physiological conditions.

A smart cell that reacts to its environment

Here, researchers manufacture a new class of DNA-based artificial cells that can communicate with neurons to promote the differentiation of neural stem cells. The smart pharmaceuticals aren’t alive but are taken from pieces of biological entities to biomimic a living cell. At the same time, they are unable to reproduce and decompose shortly after use.

Primarily the synthetic cells are created using a phospholipid vesicle which houses fat molecules and DNA. Inside the artificial vesicle or cell, the DNA reacts to specific molecules in its environment which causes it to manufacture brain-derived neurotrophic factor (BDNF), a DNA transcription regulator known as LuxR, and, PFO, a cholesterol-dependent toxin.

As a result, when the correct molecules are detected in the extracellular environment LuxR reacts with a molecule involved in quorum signaling to make the PFO form pores in the cholesterol-based outer shell. BDNF, a key molecule involved in plastic changes related to learning and memory, must also be present for this reaction to occur. This means the BDNF is only produced when the correct molecules are present in the extracellular environment. So that, BDNF is only released from the synthetic cell via the PFO pores in the presence of LuxR and the quorum signaller.

Results show the BDNF produced a signal which led murine neural stem cells to differentiate into neurons. Likewise, the smart cells also successfully communicated with engineered human embryonic kidney cells. Furthermore, all of this was achieved under physiological conditions.

What next for smart pharmaceuticals?

The lab states their new synthetic biological technique enables in situ synthesis and on-demand release of chemical signals. It is in this way, these smart pharmaceuticals could elicit somatic changes of eukaryotic cells, including neuronal differentiation, as required. They go on add that their work has enabled future theoretical science to begin to bleed into the present. For this reason, in vivo trials can now begin to develop smart pharmaceuticals and other astrobiological lifeforms.

In summary, if they can engineer artificial cells that are safe to use in a living organism, can sense their surroundings, and release chemical signals as and when needed to control natural cells, the group feels this could be a very effective therapy.

The team surmises they have manufactured an artificial cell that can react and interact with native cells under physiological conditions. Additionally, the smart cells successfully communicated with naturally-occurring cells to elicit somatic changes. For the future, the researchers state artificial cells such as theirs could be engineered to synthesize and deliver specific therapeutic molecules tailored to distinct living systems or illnesses whilst in the body.


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