Scientists Develop Drug-Delivering ‘Nanodrills’ that Penetrate Cell Membranes

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Researchers have created new drill-shaped nanomaterials that infiltrate cellular membrane and deliver drugs inside the cell, providing a versatile means to increase potency of therapeutics. Their work is published in the Journal of Controlled Release.

Ashwanikumar et al have developed a drug delivery system using cell-penetrating self-assembling peptide nanomaterials (CSPNs); these drilled-shaped nanomaterials traverse cellular membranes to deliver drugs and can be fine-tuned into different shapes to optimize delivery. Image credit: Ashwanikumar et al, doi: 10.1016/j.jconrel.2018.02.041.

Ashwanikumar et al have developed a drug delivery system using cell-penetrating self-assembling peptide nanomaterials (CSPNs); these drilled-shaped nanomaterials traverse cellular membranes to deliver drugs and can be fine-tuned into different shapes to optimize delivery. Image credit: Ashwanikumar et al, doi: 10.1016/j.jconrel.2018.02.041.

Developing effective therapeutic drugs is an arduous process that involves a large investment of time and money even before clinical trials begin.

Often, drugs that should theoretically treat a disease do not reach clinical trials because the drugs fail to penetrate biological barriers such as cellular membranes and reach the desired molecular target.

Scientists at Oregon State University have developed a new nanomaterial that facilitates the delivery of drugs through cell membrane which they call CSPNs, or cell-penetrating self-assembling peptide nanomaterials.

Composed of amino acids that self-assemble into a shape akin to a drill bit, these nanostructures can encapsulate drugs to deliver into the cell after infiltrating the membrane. CSPNs are also highly versatile for modification to accommodate for specific pharmacological needs.

“CSPNs represent a new modular drug delivery platform that can be programmed into exquisite structures through sequence-specific fine-tuning of amino acids,” said study leader Gaurav Sahay.

“The fine-tuning of amino acids imparted versatile properties like flexibility, self-assembly, higher drug loading, biodegradability and biocompatibility for effective intracellular delivery of CSPNs.”

The researchers tested the structure and function of 5 different CSPNs, which they built by conjugating peptides with a (RADA)2 linker and altering the number of phenylalanine residues they included.

“We chose (RADA)2 because it contains alternating amino acids that repel water and mix with water; that imparted the property of self-assembly,” commented primary author Ashwani Narayana.

“We demonstrated the transition of secondary structure in these CSPNs, which in turn played a vital role in self-assembly and drug delivery potential. The in-vivo efficacy of these nanodrills will extend the frontiers beyond intracellular delivery,” Naryana added.

Interestingly, they found the CSPNs shape changed from a coarse-twisted to a fine-twisted nanodrill morphology as they added more phenylalanine residues.

The coarse-twisted drill efficiently delivered rapamycin, a drug known to induce autophagy, the recycling of cellular components.

“These nanodrills had a high capacity to encapsulate hydrophobic guest molecules,” Narayana said. “The coarse-twisted nanodrills in particular demonstrated higher internalization and were able to localize rapamycin in the liver in a mouse model.”

“These modular CSPNs could be a new platform for delivering molecules across biological barriers thought to be impenetrable. And minute changes can direct self-assembly into myriad defined nanostructures, making them ideal hosts for a range of different molecules,” Sahay concluded.

This technology may play an integral role in drug delivery in the future.

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N. Ashwanikumar et al. Supramolecular self assembly of nanodrill-like structures for intracellular delivery. Journal of Controlled Release, published online March 1, 2018; doi: 10.1016/j.jconrel.2018.02.041