Easy Shape Control Comes to Drug-Delivery Nanoparticles

Look! Under the microscope! It’s an ellipsoid. It’s a tube. It’s a nonspherical drug-delivery vehicle. More specifically, it’s a perylene-containing polymersome, a nanoparticle with powers and abilities beyond those of normal nanocarriers. Normal nanocarriers are either spherical or capable of one type of nonspherical shape. Pereylene-containing polymersomes, however, can self-assemble into a range of morphologies,depending on parameters as easily controlled as solvent composition.

The powers and abilities of this new kind of nonspherical nanoparticle may go beyond shapeshifting. It may, compared to the spherical nanoparticle, improve drug delivery. Nonspherical nanoparticles may load drugs more readily, attach to the walls of target cells more tenaciously, and be taken up by cells more efficiently.

Pereylene-containing polymersomes have been developed by scientists based at the University of New South Wales (UNSW). The scientists worked with polymer molecules that contain a water-soluble portion and a non-water-soluble portion, and that self-assemble into round, hollow structures in solution.

These structures, called polymersomes, are emerging as powerful new tools to deliver drugs to the desired part of the body due to their high stability, chemical versatility, and the ease with which molecules on their surface can be altered. Their full potential, however, has been hindered by the difficulty of controlling their shape.

The UNSW scientists, led by Pall Thordarson, Ph.D., pioneered a new polymerosome approach, which they described November 1 in the journal Nature Communications, in an article entitled “Formation of Non-Spherical Polymersomes Driven by Hydrophobic Directional Aromatic Perylene Interactions.”

“Here we show that a range of non-spherical polymersome morphologies with anisotropic membranes can be obtained by exploiting hydrophobic directional aromatic interactions between perylene polymer units within the membrane structure,” wrote the article’s authors. “By controlling the extent of solvation/desolvation of the aromatic side chains through changes in solvent quality, we demonstrate facile access to polymersomes that are either ellipsoidal or tubular-shaped.”

Essentially, the UNSW team added a non-water-soluble perylene polymer group to the membrane of the polymersome. Then the team adjusted the shape and size of the polymersome by changing the amount of water in the solvent. The team also used cryogenic transmission electron microscopy—the technique for which the 2017 Nobel Prize in Chemistry was awarded—to determine how the polymer molecules were packed together in solution.

“Very little in nature is perfectly spherical,” said Thordarson. “Most biological structures, like cells, bacteria, and viruses, come in a variety of shapes, including tubes, rods, and squashed spheres, or ellipsoids. But it has proved very difficult for scientists to synthesize particles that are not perfectly round.

“Our breakthrough means we can predictably make smart polymers that shift their shape according to the different conditions around them to form tiny ellipsoidal or tubular structures that can encapsulate drugs.”

“We have preliminary evidence that these more natural-shaped plastic nanoparticles enter tumor cells more easily than spherical ones,” he added.

“Extensive characterization of the polymersomes by means of spectroscopy and microscopy further revealed that not only do these polymersomes possess non-spherical shapes, but also unusual membrane properties,” the Nature Communications article noted. “The use of perylene aromatic interactions to direct the self-assembly of amphiphilic polymers is, in our opinion, a straightforward but elegant method for the fabrication of a variety of non-spherical polymersomes and other structurally unusual self-assembled polymer systems.”

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Easy Shape Control Comes to Drug-Delivery Nanoparticles

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