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WIREs Nanomed Nanobiotechnol
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Targeted nanoparticles in mitochondrial medicine

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Mitochondria, the so‐called ‘energy factory of cells’ not only produce energy but also contribute immensely in cellular mortality management. Mitochondrial dysfunctions result in various diseases including but not limited to cancer, atherosclerosis, and neurodegenerative diseases. In the recent years, targeting mitochondria emerged as an attractive strategy to control mitochondrial dysfunction‐related diseases. Despite the desire to direct therapeutics to the mitochondria, the actual task is more difficult due to the highly complex nature of the mitochondria. The potential benefits of integrating nanomaterials with properties such as biodegradability, magnetization, and fluorescence into a single object of nanoscale dimensions can lead to the development of hybrid nanomedical platforms for targeting therapeutics to the mitochondria. Only a handful of nanoparticles based on metal oxides, gold nanoparticles, dendrons, carbon nanotubes, and liposomes were recently engineered to target mitochondria. Most of these materials face tremendous challenges when administered in vivo due to their limited biocompatibility. Biodegradable polymeric nanoparticles emerged as eminent candidates for effective drug delivery. In this review, we highlight the current advancements in the development of biodegradable nanoparticle platforms as effective targeting tools for mitochondrial medicine. WIREs Nanomed Nanobiotechnol 2015, 7:315–329. doi: 10.1002/wnan.1305

Multi‐walled carbon nanotube‐based mitochondria‐targeted drug delivery vehicle (Redrawn based on Ref ).
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PAMAM dendrimers for mitochondria‐targeted gene delivery (Redrawn based on Ref ). PAMAM, poly(amidoamine); TPP, triphenylphosphonium.
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PAMAM dendrimers for mitochondria‐targeted delivery. PAMAM, poly(amidoamine).
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Chemical structure of DQA and its self‐assembly into liposome‐like vesicles (Redrawn based on Ref ). DQA, dequalinium (1,1′‐decamethylene bis(4‐aminoquinaldiniumchloride); TPP cation, triphenylphosphonium cation.
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Evolution of nanomedicine (top) and nanotechnology approaches to mitochondrial medicine (bottom). DQA, dequalinium (1,1′‐decamethylene bis(4‐aminoquinaldiniumchloride); TPP cation, triphenylphosphonium cation.
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The structure of a mitochondrion. OMM, outer mitochondrial membrane; IMS, intermembrane space; IMM, inner mitochondrial membrane.
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Mitochondria‐targeted NPs for photodynamic therapy localized to mitochondria and mechanism of action for light triggered immune activation (Redrawn based on Ref ). DC, dendritic cell; NP, nanoparticle; PLGA, poly(lactic‐co‐glycolic acid); PEG, polyethylene glycol; ROS, reactive oxygen species; TPP, triphenylphosphonium; PS, photosensitizer.
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Mitochondria‐targeted NP system based on PLGA‐b‐PEG‐TPP for entrapment of various mitochondria‐acting therapeutics (Redrawn based on Ref ). NP, nanoparticle; PLGA, poly(lactic‐co‐glycolic acid); PEG, polyethylene glycol; TPP, triphenylphosphonium.
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Precise engineering of polymeric NPs to control NP size and surface charge for effective mitochondria‐targeting properties (top) and mitochondrial localization of targeted‐NPs and cytosolic distribution of non‐targeted NPs (bottom) (Redrawn using original data from Ref ). NP, nanoparticle; PLGA, poly(lactic‐co‐glycolic acid); PEG, polyethylene glycol; TPP, triphenylphosphonium.
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Mitochondria‐targeting polymer from PCL‐PEG modified with a linker containing TPP between PCL and PEG (Drawn based on Ref ). PCL, polycaprolactone; PEG, polyethylene glycol.
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Mitochondria‐targeted liposomal nanocarriers for drug delivery. A generalized figure to indicate that mitochondria‐targeted liposomes have the ability to escape endosomes to enter the mitochondria. TPP, triphenylphosphonium.
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Carbon nanotube‐based drug delivery to mitochondria (Redrawn based on Ref ).
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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Mauro Ferrari

Mauro Ferrari

started out in mechanical engineering and became interested in nanotechnology with his studies on nanomechanics and nanofluidics. His research work and involvement with setting up some of the premier nano centers and alliances in the world, bringing together universities, hospitals, and federal agencies, showcases interdisciplinarity at work.

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