Formulation and optimization of mitochondria-targeted polymeric nanoparticles.

Targeted delivery of therapeutics to the mitochondria of cells without alteration of drug properties can be a vital technique in the treatment of a variety of mitochondrial-dysfunction-related diseases. Herein, we describe a detailed protocol for synthesis and characterization of a functionalized polymer to build mitochondria-targeted nanoparticles (NPs). The block polymer was decorated with a lipophilic triphenylphosphonium (TPP) cation for mitochondrial trafficking of payload-loaded polymeric NPs. TPP-based lipophilic cations have the ability to cross the mitochondrial membrane. A mitochondria-targeted block copolymer poly(DL-lactide-co-glycolide)-b-polyethylene glycol-TPP and a nontargeted poly(DL-lactide-co-glycolide)-b-polyethylene glycol polymer were synthesized and their NPs were prepared. A nanoprecipitation method combined with polymer blending technology was adopted in order to get suitable size and charged NPs for efficient mitochondrial trafficking.