The ability of nanoparticles (NPs) to accumulate in tumors as a result of the enhanced permeability and retention effect (EPR) is an advantageous feature for delivery of therapeutics. However, efficient drug delivery is dependent on the ability of NPs to mediate specific delivery to the subcellular site of action. Lipophilic cationic complexes, such as triphenyl phosphine (TPP) have shown to accumulate inside the mitochondria.  We have initiated an engineering approach to combine the organelle-targeting property of TPP with EPR effect of NPs by functionalizing the surface of gold NPs with a dendron conjugated to three TPPs and an inhibitor of mitochondrial hexokinase, 3-bromopyruvate. The efficiency in targeting mitochondria by the NPs carrying multivalent TPP will be compared with the NPs with monovalent ligands. The utility of these constructs in the mitochondria-targeted combination therapy will be discussed. These results will provide guidance for the development of targeted NPs with multivalent ligands.

Mitochondria-targeted gold nanoparticles for combined photothermal and chemotherapy

243rd National Meeting (2012)

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