Brown University researchers have developed a novel nanotechnology approach that could transform treatment for drug-resistant fungal infections, particularly those caused by increasingly problematic Candida species.
The research team, led by Professor Anita Shukla from Brown's School of Engineering, has successfully engineered liposomes—tiny lipid-based nanoparticles—that specifically target fungal cells, dramatically increasing drug effectiveness against resistant pathogens while sparing healthy human tissue.
Targeting the Growing Threat of Resistant Fungal Infections
Candida species normally exist harmlessly in the human body but can become life-threatening for immunocompromised individuals, including cancer patients, transplant recipients, and those in intensive care units. The emergence of drug-resistant strains, particularly Candida auris, has created an urgent need for more effective treatments.
"Fungal infections can be extremely difficult to treat and the drugs at doctors' disposal are limited," explained Veronica LaMastro, the study's lead author and recent Ph.D. graduate in biomedical engineering at Brown. "By adding a targeting peptide on the surface of liposomes, we can better target the delivery of an anti-fungal drug to fungal cells, and increase its ability to kill those cells."
C. auris has emerged as a particularly concerning "superbug," with infections increasing more than 300% in the United States between 2017 and 2018 alone. Its resistance to multiple antifungal medications has alarmed healthcare systems worldwide.
How the Technology Works
The breakthrough lies in the team's method of "decorating" liposomes with penetratin, a peptide (short chain of amino acids) that naturally attracts to Candida cells. These peptides function as molecular homing devices, helping the drug-carrying liposomes recognize and bind specifically to fungal cells.
After screening several targeting peptides, the researchers determined that penetratin demonstrated the highest effectiveness in targeting Candida. The team then synthesized liposomes decorated with penetratin and loaded with posaconazole, an FDA-approved antifungal drug currently used prophylactically to prevent Candida overgrowth.
Remarkable Efficacy in Laboratory Testing
Laboratory experiments revealed impressive results. The targeted liposomes:
- Interacted significantly more with Candida cells than standard liposomes
- Inhibited Candida growth at concentrations up to eight times lower than free posaconazole
- Prevented biofilm formation at doses up to 1,300 times lower than conventional treatments
- Showed no toxicity to human cells commonly affected during infection, including skin, blood vessel, vaginal tissue, and red blood cells
Biofilms—complex communities of microorganisms that adhere to surfaces—are particularly challenging to treat, as they provide fungi with protection against antimicrobial agents. The dramatic improvement in efficacy against biofilms represents a significant advancement in antifungal therapy.
Promising Results in Animal Models
To evaluate real-world effectiveness, the researchers tested their approach in a mouse model of intradermal C. albicans infection. Mice receiving the targeted liposomes showed a 60% lower fungal burden compared to those given regular drug-loaded liposomes, suggesting substantial potential for preventing fungal spread in clinical settings.
"This targeted delivery system dramatically increased the potency of the antifungal drug," LaMastro noted. "The peptides act as a molecular GPS, guiding the liposomes directly to the infection sites."
Future Directions and Broader Implications
The research, published in the journal Advanced Functional Materials and supported by the National Science Foundation, opens new avenues for combating antimicrobial resistance.
"Fungal infections are a vastly understudied area, especially in the engineering and biomaterials communities," said Professor Shukla. "But with rising antimicrobial resistance coupled to the increasing use of antifungals in clinical and agricultural settings, this type of work becomes more important. We hope more researchers will recognize that and do more work in this field."
The team now plans to expand their research by testing the targeted liposome approach with drugs used to treat established infections, rather than just preventative applications.
This innovative technology could potentially be adapted to target other drug-resistant pathogens, offering a versatile platform to address the growing global challenge of antimicrobial resistance through precision-targeted therapeutics.
