NANOMEDICINES
Polymer nanoparticles mimic bacteriophages Particles could lead to therapies that fight infections while avoiding antibiotic resistance stick out from the cores of these particles. The team tested the ability of the fuzzy nanoparticles to kill Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and various multi-drug-resistant bacteria. They also studied the particles’ toxicity to human cells. The spherical particles worked best, killing over 99.9% of both Gram-positive and Gram-negative bacteria. They showed remarkable potency against multi-drug-resistant Pseudomonas aeruginosa. The longer particles showed lower antibacterial activity but were more deadly to Gram-negative bacteria than to Gram-positive ones. “We can tune antibiotic activity just by changing the size and shape,” Liang says. Unlike antimicrobial peptides or their synthetic mimics, these polymer particles are not lethal to human cells. That’s because the particles rely on the shapes of lipids within cell apart bacteria, avoiding the Escherichia coli bacteria membranes to inflict dambiological mechanisms that (left) incubated with age. Bacterial membranes commonly trigger bactespherical polymer are rich in phosphoethanolnanoparticles suffer ria to develop resistance. amine lipids, which have an cell membrane damage These positively charged, intrinsic curve, so they eas(right). amphiphilic peptides ily bend and wrap around bind tightly to negatively the nanoparticles’ bristles, straining the charged lipid molecules to rupture cell membrane and causing the cell to burst. membranes. But the hydrophobic parts of such peptides can also disrupt mammalian Meanwhile, human cells are primarily cell membranes, limiting their potential as made of flat phosphocholine lipids. The particles can’t rupture those more rigid new antibiotics. Hongjun Liang of Texas Tech University membranes. It’s an exciting new approach to antithought that bacteriophages—viruses that infect bacteria—might offer strategies that microbials, says Jacinta C. Conrad of the could make antimicrobial peptides or their University of Houston. “This could be the critical new tool needed to fight drug-repolymer mimics more selective. “We were sistant bacteria, which may not be killed curious what role the phage nanostrucby other means.” tures play,” he says. Liang cautions that his team will have Liang and colleagues made three difto go back and design nanoparticles made ferent polymer nanoparticles that mimic of polymers that are more biocompatible the hairy surfaces of bacteriophages: an and biodegradable. “We should go back 8-nm-wide sphere and two 7-nm-wide to the drawing board and come up with rod-shaped particles that were 18 nm and 70 nm long, respectively. Hundreds of posi- something that has a good chance of tively charged, hydrophilic bristles made of passing rigorous safety tests.”—PRACHI poly(4-vinyl-N-methylpyridinium iodide) PATEL, special to C&EN
C R E D I T: ACS I N F ECT. D I S .
Viruslike polymer nanoparticles can target and kill different types of bacteria—including antibiotic-resistant strains—while sparing human cells, according to a new study (ACS Infect. Dis. 2017, DOI: 10.1021/acsinf ecdis.7b00076). What’s more, fine-tuning the size and shape of these fuzzy particles alters their potency. The strategy could represent a step toward a new class of antimicrobials that fights infections while avoiding antibiotic resistance. Many scientists have been working on possible therapies based on naturally occurring peptides that physically rip
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SEPTEMBER 4, 2017 | CEN.ACS.ORG | C&EN
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