ROS-responsive nanoliposomes loaded with anti-oomycetes medium-chain fatty acids for shuttling delivery in plant disease control

BACKGROUND: 2E,4E-decadienoic acid (DDA) is an aliphatic compound with potent anti‑oomycete activity against Phytophthora nicotianae (Pn), a plant pathogen responsible for major agricultural losses. Mechanistic studies revealed that DDA targets mitochondria and requires intracellular delivery to exert its activity. To improve its stability and bioavailability, we developed a reactive oxygen species (ROS)-responsive, TAT‑peptide (P) ‑modified liposomal (Lipo) delivery system (DDA@P‑ROS‑Lipo) containing thioketal (TK) linkages that cleave under elevated ROS conditions during pathogen infection, enabling controlled and site‑specific release of DDA. The TAT peptide, as a cell‑penetrating moiety, markedly enhanced intracellular uptake. RESULTS: The resulting nanoparticles exhibited an average hydrodynamic diameter of approximately 112 nm and a high DDA encapsulation efficiency of 80.84%. They also demonstrated excellent photostability, making the formulation suitable for field application. The nanoscale size and strong affinity for tobacco leaf surfaces reduced the contact angle, thereby improving adherence and deposition. Compared with free DDA, the nanoformulation enhanced mycelial inhibition by 45% and achieved superior control of tobacco black shank disease in pot experiments. Both in vitro cytotoxicity and in vivo zebrafish toxicity assays confirmed the safety of the formulation. CONCLUSION: This work presents a simple and effective strategy for the targeted delivery of anti‑oomycete agents. DDA@P‑ROS‑Lipo offers a green and efficient approach for plant disease management under controlled conditions, and future studies will explore its scalability and performance in field environments.