Artificial cells can deliver molecules better than the real thing

With an onion-like structure, the artificial cells developed by researchers at Penn appear more stable and better equipped to carry cargo than their natural and commercial counterparts.

Far left is chemical with phenol rings and long carbon chains, underneath are red circles showing the onion-like structure. Center panel shows a protein structure with a fluorescent tag marked by a green star, labeled with benzyl-guanine, SNAP protein, DNA Aptamer, FAM dye, His-tag, NI2+, and RH-NTA. Last figure shows the same protein in the center replicated many times to form a circular structure.
Chemical components of the dendrimer (left), which self-assemble into an onion-like artificial cell (in red). A detailed depiction of the additional proteins and DNA cargos (center) that are conjugated to artificial cell (right). (Image courtesy: Paola Torre)

From pills to vaccines, ways to deliver drugs into the body have been constantly evolving since the early days of medicine. 

Now, a new study from an interdisciplinary team led by researchers at the University of Pennsylvania provides a new platform for how drugs could be delivered to their targets in the future. Their work was published in the Proceedings of the National Academy of Sciences.

The research focuses on a dendrimersome, a compartment with a lamellar structure and size that mimic a living cell. It can be thought of as the shipping box of the cellular world that carries an assortment of molecules as cargo.

The scientists found that these dendrimersomes, which have a multilayered, onion-like structure, were able to “carry” high concentrations of molecules that don’t like water, which is common in pharmaceutical drugs. They were also able to carry these molecules more efficiently than other commercially available vessels. Additionally, the building block of the cell-like compartment, a janus dendrimer, is classified as an amphiphile, meaning it contains molecules that don’t like water and also molecules that are soluble in water, like lipids, that make up natural membranes.

“This is a different amphiphile that makes really cool self-assembled onions into which we were able to load a bunch of molecular cargos,” says co-author Matthew Good.

Part of what makes the dendrimersome special is its construction from artificial materials. The researchers used organic polymers to build them from scratch, creating a vessel that is tough and versatile, but that also acts like a membrane in an actual living cell. Most commercially available systems, often made from fats rather than monodisperse polymers known as amphiphilic Janus dendrimers, only remain stable for a few days at a time. Study co-author Qi Xiao and other members of the lab of Virgil Percec have constructed vesicles that have stayed stable for months to even years.

“They're ultra-stable in serum and they retain the cargoes loaded on or in them, which is kind of the proof-of-concept that they should, in theory, also be more stable in a living organism [than commercially available vesicles],” Good says.

Creating this non-natural cell is one approach to understanding exactly how cells function in nature and the role that each part of a cell plays. Because the natural cells are significantly less stable, artificial cell models allow researchers a simplified model with which to test theories and explore the deeper intricacies of how cells work.

This research is still in the early stages, but one possible avenue for continued study is testing how viable this drug delivery system can be in living systems and to see what else needs to be improved before going to market. Good also speculates that in the future hybrid cells could be created with components of both natural and non-natural cells, enhancing the stability of cells found in nature.

“Almost everything in biology happens in the cell. But the cell is complicated, and it is difficult to quantitatively describe its biology, in part because we cannot easily reconstitute it,” Percec says. “We hope to build models that may not be identical [or] exactly like the natural ones but close enough that we can slow down some of the dynamics and understand the kind of things that are hard to decipher in natural systems.”

The research was supported by the National Science Foundation (grants DMR-1066116, DMR- 1807127, DMR-1120901,and  DMR-1720530), P. Roy Vagelos Chair at the University of Pennsylvania, Alexander von Humboldt Foundation, and Burroughs Wellcome Fund.

Virgil Percec is the P. Roy Vagelos Professor of Chemistry in the Department of Chemistry in the School of Arts and Sciences at the University of Pennsylvania.

Matthew Good is an assistant professor of cell and developmental biology in the Perelman School of Medicine and of bioengineering in the School of Engineering and Applied Science, both at the University of Pennsylvania.

Other Penn researchers involved with this work include Paola Torre, Irene Buzzacchera, and Samuel E. Sherman.

This work was done in collaboration with Temple University, the DWI-Leibniz Institute for Interactive Materials, NovioSense, and Aachen University.