Delivery of drugs and macromolecules to the mitochondria for cancer therapy.
Mitochondria are organelles that have pivotal functions in producing the energy necessary for life and executing the cell death pathway. Targeting drugs and macromolecules to the mitochondria may provide an effective means of inducing cell death for cancer therapy, and has been actively pursued in the last decade. This review will provide a brief overview of mitochondrial structure and function, how it relates to cancer, and importantly, will discuss different strategies of mitochondrial delivery including delivery using small molecules, peptides, genes encoding proteins and MTSs, and targeting polymers/nanoparticles with payloads to the mitochondria. The advantages and disadvantages for each strategy will be discussed. Specific examples using the latest strategies for mitochondrial targeting will be evaluated, as well as potential opportunities for specific mitochondrial compartment localization, which may lead to improvements in mitochondrial therapeutics. Future perspectives in mitochondrial targeting of drugs and macromolecules will be discussed. Currently this is an under-explored area that is prime for new discoveries in cancer therapeutics.
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, 30 S. 2000 E., University of Utah, Salt Lake City, UT 84112, USA.
Phong
P
Lu
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, 30 S. 2000 E., University of Utah, Salt Lake City, UT 84112, USA.
Benjamin J
BJ
Bruno
Department of Pharmaceutics and Biopharmacy, Phillips-Universität, 35037 Marburg, Germany.
Malena
M
Rabenau
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, 30 S. 2000 E., University of Utah, Salt Lake City, UT 84112, USA. Electronic address: carol.lim@pharm.utah.edu.
Carol S
CS
Lim
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D046911:Macromolecular Substances / Q000008:administration & dosage / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism
D000970:Antineoplastic Agents; D046911:Macromolecular Substances; D004364:Pharmaceutical Preparations
Bcl-2 family; Delocalized cations; Intrinsic apoptosis; Mitochondrial import; Mitochondrial targeting signal (MTS); p53