Potential-Independent Mitochondrial Targeting
Abstract
Mitochondria are a vital organelle supporting a wide range of biological processes. Mitochondrial defects or dysfunctions result in many human diseases and disorders. Mitochondria are one of the most important therapeutic targets, and selective delivery of therapeutics or imaging probes to mitochondria is highly desirable for studying mitochondrial functions and treating mitochondrial diseases. Unfortunately, mitochondria are difficult to access for many therapeutics due to their unique structures and functions. The current mitochondrial targeting strategies mainly rely on the binding affinity between the negatively charged mitochondria and positively charged targeting ligands. However, it is known that the mitochondrial membrane potential (charge), a key indicator of mitochondrial health, is not always constant in the cell life cycle, particularly under drug treatments, which may greatly influence the effectiveness of these potential-dependent strategies. Furthermore, the positive charge of current mitochondrial targeting ligands is not always favorable to biomedical applications and may cause undesirable side effects. In this application, the novel charge-neutral polymers are proposed as nanocarriers for potential-independent mitochondrial targeting. Unlike the potential-driven targeting strategies, the proposed strategy will not influence the mitochondrial potential or be influenced by the mitochondrial potential. Therefore, it will be more reliable for various biomedical applications. If successful, the proposal will (i) provide the first potential-independent tool for reliable mitochondrial imaging and targeting, (ii) promote the clinical translation of mitochondria-acting drugs, and (iii) be a new strategy for repurposing other types of drugs for treating mitochondrial diseases. The proposed strategy will advance the diagnosis and treatment of mitochondrial diseases and will ultimately benefit the military Service Members, Veterans, and their beneficiaries as well as other people who are suffering from mitochondrial diseases (one of the Fiscal Year 2022 Peer Reviewed Medical Research Program Topic Areas and Strategic Goals).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310119
Entities
People
- Zhu Lin
Organizations
- Texas A&M Health Science Center
- United States Army