Mitochondria-targeted nanocarriers for smart response delivery of natural products: a review

:Mitochondrial dysfunction is closely associated with the onset and progression of various major diseases, including cancer and neurodegenerative disorders. The design of smart nanomaterial-natural product composite systems offers an innovative strategy for multifunctional nanocarriers. These smart carriers not only enable precise, controlled release of active components at specific mitochondrial targets but also provide novel technical support for natural products to overcome various barriers encountered during in vivo administration, thereby enhancing bioavailability. This review systematically summarizes the latest research advances in mitochondria-targeted nano-drug delivery systems based on smart responsive principles for delivering natural products. It focuses on exploring the design principles, mechanisms of action, and representative applications of various responsive systems (including pH-, enzyme-, redox-, temperature-, light-, magnetic-, and ultrasound-responsive systems). Furthermore, existing challenges and unexplored therapeutic opportunities through interdisciplinary strategies integrating AI technology, CRISPR gene editing, and biomimetic materials are also highlighted and discussed to inspire the next generation of mitochondrial-targeted nanotherapeutics.