Tiny particles made from the membranes of human immune cells could offer a promising new way to fight fungal infections that are becoming harder to treat, according to a July 9 report. Engineers at the University of California San Diego created antifungal nanoparticles that target Candida albicans, a fungus responsible for oral and vaginal yeast infections as well as life-threatening bloodstream infections. In mice with severe Candida infections, the nanoparticles greatly reduced the amount of fungus in major organs and significantly improved survival.
The research, published in Cell Biomaterials, was led by Liangfang Zhang, professor in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at the UC San Diego Jacobs School of Engineering. Zhang also holds the Joan and Irwin Jacobs Chancellor's Endowed Chair in Innovations for Engineering in Medicine.
Antifungal medications today typically target specific parts of a fungal cell and can lose effectiveness as fungi evolve resistance. The nanoparticles developed by Zhang's team use a different strategy: "They physically damage fungal cells and, at the same time, boost the body's natural immune defenses."
To create these nanoparticles, researchers isolated outer membranes from human macrophages—a type of white blood cell—and fused them onto disc-shaped biodegradable polymer particles. These nanodiscs retain proteins used by macrophages to recognize and attack fungi. As described by Zhang's team, "They essentially behave like miniature versions of the body's own immune cells themselves, which also allows them to evade attack by the immune system." The nanodiscs are covered with receptors that naturally recognize Candida; this enables them to attach more effectively than other nanoparticle types.
Once attached to fungal cells, these nanodiscs weaken their protective outer membrane until openings form—causing cell contents to leak out and ultimately killing the fungus. Researchers believe this physical damage approach may make it much harder for fungi like Candida albicans to evolve resistance compared with drugs targeting specific molecules.
The treatment was tested on mice with severe bloodstream infections caused by Candida. Treated mice had far less fungus present in major organs such as heart, kidneys, lungs and spleen; their survival rates improved significantly compared with untreated mice—at higher doses all treated animals survived. The treatment was also effective when administered before infection occurred.
Researchers plan next steps including further evaluation against additional highly pathogenic fungal species.
