Probiotics face two major challenges in clinical applications: limited long-term survival in pathological environments due to weak defense mechanisms, and the production of a narrow range of functional metabolites at low concentrations, which restricts their therapeutic potential. Fangfang Cao focuses on integrating biomimetic materials with microbes to engineer next-generation probiotics with enhanced resilience and efficacy.
She proposed the concept of biomimetic editing of probiotics using antioxidant nanozymes. By constructing an antioxidant nanozyme–probiotic hybrid system, she endowed probiotics with strong oxidative stress resistance, thereby solving the survival challenge in inflammatory environments. She validated the therapeutic effects in a large-animal (canine) model, where just three days of oral administration led to significant improvement in ulcerative colitis. She is also working with Zeria Pharmaceutical, a Japanese company, to advance preclinical evaluation and clinical translation of the technology.
To boost the anti-tumor metabolic capacities of probiotics, Fangfang proposed a complementary strategy using pro-oxidative nanozymes. She built a pro-oxidative nanozyme–probiotic hybrid system that selectively generates non-lethal levels of hydroxyl radicals in the tumor microenvironment. This promotes the natural production of tumor-suppressive short-chain fatty acids (SCFAs) by the probiotics.
The resulting SCFAs lower the local pH, which in turn further enhances nanozyme activity and reactive oxygen species (ROS) generation, producing a positive feedback loop that enables effective treatment of colorectal cancer.