Human beta-defensin 3-functionalized Fe/GMP nanozyme for multifunctional antimicrobial and anticancer activity
Yoganathan Kamaraj1, Veenayohini Kumaresan2, Jinhao Hu1
1Biofuels Institute, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Jiangsu Collaborative Innovation Center of Technology and Material of Water Treatment, Suzhou University of Science and Technology, Suzhou 215009, China.
Background:
The rising incidence of Helicobacter pylori-associated infections and colorectal cancer necessitates multifunctional therapeutics targeting both microbial and tumor pathologies. However, antimicrobial peptides (AMPs) like human β-defensin 3 (hBD-3) faces challenges such as proteolytic degradation and poor bioavailability. To address these limitations, we developed a novel hybrid nanozyme by immobilizing hBD-3 onto a guanosine monophosphate-coordinated iron framework (Fe/GMP), known for its biocompatibility and intrinsic peroxidase-like activity.
Methods:
The hBD-3@Fe/GMP nanozyme was synthesized and characterized for its physicochemical and catalytic properties. Its antibacterial activity against H. pylori was assessed via agar diffusion, biofilm inhibition, and virulence gene expression. Anti-colon cancer potential was evaluated in HT-29 cells using assays for cytotoxicity, ROS generation, apoptosis, migration inhibition, and redox biomarkers. in vivo antitumor efficacy was studied using a colon carcinoma xenograft mice model.
Results:
hBD-3@Fe/GMP showed enhanced peroxidase-like activity with elevated ROS production than Fe/GMP alone. It significantly inhibited H. pylori growth, biofilm formation, and virulence gene expression (babA, alpA, alpB, flaA, flaB). In HT-29 cells, it induced cytotoxicity, suppressed antioxidant enzymes, and triggered apoptosis via p53 and Bax upregulation and Bcl-2 downregulation. In tumor xenograft model, it reduced tumor volume and weight.
Conclusion:
This study reports, for the first time, a hybrid nanozyme that synergistically integrates the antimicrobial potency of hBD-3 with the catalytic redox functionality of Fe/GMP, offering dual action against H. pylori infection and colorectal cancer. The multifunctional therapeutic potential and biocompatibility of hBD-3@Fe/GMP mark a novel paradigm in the development of next-generation nanozymes for combinatorial infectious and oncological interventions.
Insights
A new hybrid nanozyme combines human beta-defensin 3 (hBD-3) with an iron framework (Fe/GMP) for dual action against H. pylori infections and colorectal cancer. This nanozyme shows potent antimicrobial and antitumor effects, offering a promising therapeutic strategy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Therapeutics Development
Background:
- Rising incidence of H. pylori infections and colorectal cancer requires novel dual-action therapies.
- Antimicrobial peptides (AMPs) like hBD-3 face bioavailability and degradation issues.
- Development of hybrid nanozymes offers a solution to overcome AMP limitations.
Purpose of the Study:
- To synthesize and characterize a novel hybrid nanozyme (hBD-3@Fe/GMP) for combined antimicrobial and anticancer activity.
- To evaluate the nanozyme's efficacy against H. pylori infection and colorectal cancer.
- To explore the nanozyme's mechanism of action in vitro and in vivo.
Main Methods:
- Synthesis and characterization of hBD-3@Fe/GMP nanozyme.
- Assessment of antibacterial activity against H. pylori (growth, biofilm, virulence genes).
- Evaluation of anti-colon cancer potential in HT-29 cells and a mouse xenograft model.
Main Results:
- hBD-3@Fe/GMP demonstrated enhanced peroxidase-like activity and ROS production.
- Significant inhibition of H. pylori growth, biofilm, and virulence factors observed.
- Nanozyme induced cytotoxicity, apoptosis, and suppressed migration in colon cancer cells, reducing tumor growth in vivo.
Conclusions:
- The study presents the first hybrid nanozyme (hBD-3@Fe/GMP) with synergistic antimicrobial and anticancer properties.
- hBD-3@Fe/GMP offers a multifunctional therapeutic approach for H. pylori infections and colorectal cancer.
- This nanozyme represents a novel platform for next-generation therapeutics in infectious diseases and oncology.
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