Recently, Prof. Hulin Jiang's team has published a series of research results on the use of engineered mitochondria to regulate mitochondrial homeostasis in ACS Nano (IF: 15.8), a leading engineering journal, and Acta Pharmaceutica Sinica B (IF: 14.7) and Advanced Drug Delivery Reviews (IF: 15.2), leading medical journals.
Mitochondria are key organelles in eukaryotic cells, and their dysfunction can lead to a series of mitochondrial diseases involving various tissues and organs in the body. According to the different triggers leading to mitochondrial dysfunction, mitochondrial diseases can be categorized into primary mitochondrial diseases and secondary mitochondrial diseases. Primary mitochondrial diseases are diseases caused by mutations in nuclear or mitochondrial DNA associated with mitochondrial function. Secondary mitochondrial diseases are those in which the cause of the disease does not originate directly from the mitochondria, but is characterized by mitochondrial dysfunction.
Pulmonary fibrosis (PF), a progressive and fatal interstitial lung disease closely associated with imbalance of mitochondrial homeostasis in alveolar epithelial cells, is also a classic secondary mitochondrial disease. Mitochondrial transplantation can restore mitochondrial function by delivering exogenous mitochondria. However, in the pathological state of PF, dysfunctional mitochondria cannot be effectively removed due to impaired mitochondrial autophagy, which affects the effectiveness of mitochondrial homeostasis regulation. This research team constructed a mitochondrial autophagy-enhanced nanoparticle-modified engineered mitochondria, which on the one hand, increased the proportion of healthy mitochondria in the cell by improving the efficiency of mitochondrial delivery; and on the other hand, decreased the proportion of damaged mitochondria by promoting the autophagic degradation of dysfunctional mitochondria, which jointly regulated the mitochondrial homeostasis. In a bleomycin-induced PF mouse model, engineered mitochondria effectively repaired mitochondrial function and alleviated PF symptoms. The related work was published as “Mitophage-enhanced nanoparticle-engineered mitochondria restore homeostasis of mitochondrial pool for alleviating pulmonary fibrosis” in ACS Nano. Associate researcher of the School of Pharmacy, Wang Yi, master's degree graduate, Hu Lifan, and doctoral student, Liu Nahui, are the co-first authors, and Prof. Jiang Hulin of our university and Prof. Li Ling, School of Medicine, Southeast University, are the co-corresponding authors of the paper.
Link to full article: https://doi.org/10.1021/acsnano.4c1032
Leber's hereditary optic neuropathy (LHON) is a primary mitochondrial disease caused by dysfunction of mitochondrial respiratory chain complex I, for which there is no effective treatment. The team constructed nanoengineered mitochondria to effectively restore the function of mitochondrial respiratory chain complex I, thus realizing the treatment of LHON. The related work was published as “Nanoengineered mitochondria enable ocular mitochondrial disease therapy via the replacement of dysfunctional mitochondria in Acta Pharmaceutica Sinica B. Associate researcher of School of Pharmacy, Wang Yi, PhD student, Liu Na Hui, and master's graduate, Hu Lifan, are the co-first authors, and Prof. Jiang Hulin and Associate Prof. Xing Lei are the co-corresponding authors of the paper.
Link to full article: https://doi.org/10.1016/j.apsb.2024.08.007
Based on the previous work, the team systematically summarized the mitochondria-targeted gene delivery systems inspired by the mitochondrial endogenous substance transport pathway, including nanomaterials inspired by the mitochondrial steroid hormone import pathway, nanomaterials inspired by the protein translocation pathway, and other mitochondria-targeted gene delivery nanomaterials, and introduced in detail the design concept of the mitochondria-targeted delivery systems and the challenges they face. The related work was published as “Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery” The related work was published in Advanced Drug Delivery Reviews under the title of “Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery”. Associate researcher of School of Pharmaceutical Sciences, Wang Yi, master's student Yang Jingsong, and doctoral student Zhao Min are the co-first authors, and Prof. Jiang Hulin is the sole corresponding author of this paper.
Link to full article: https://doi.org/10.1016/j.addr.2024.115355
The team will further focus on the treatment of mitochondrial diseases and actively promote the translation of basic research into scientific and technological achievements. The above work was funded by the Key R&D Program of the Ministry of Science and Technology, the Key International (Regional) Cooperative Research Program of the National Natural Science Foundation of China (NSFC), the Youth Fund of the NSFC, and the State Key Laboratory of Active Components and Efficacy of Natural Drugs of China Pharmaceutical University.
