Targeted nanoparticles in mitochondrial medicine

Abstract

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.

Figure 1

The structure of a mitochondrion. OMM: Outer mitochondrial membrane, IMS: intermembrane space, IMM: inner mitochondrial membrane.

Figure 2

Evolution of nanomedicine (top) and nanotechnology approaches to mitochondrial medicine (bottom). DQA: dequalinium (1,1′-decamethylene bis (4-aminoquinaldiniumchloride), TPP cation: triphenylphosphonium cation.

Figure 3

Chemical structure of DQA and its self-assembly into liposome-like vesicles. Redrawn based on Reference (80).

Figure 4

PAMAM dendrimers for mitochondria targeted delivery. Redrawn based on Reference (86).

Figure 5

PAMAM dendrimers for mitochondria targeted gene delivery. Redrawn based on Reference .

Figure 6

Multi-walled carbon nanotubes (MWCNTs) based mitochondria targeted drug delivery vehicle. Redrawn based on Reference .

Figure 7

Carbon nanotube based drug delivery to mitochondria. Redrawn based on Reference .

Figure 8

Mitochondria targeted liposomal nanocarriers for drug delivery. A generalized figure to indicate how the mitochondria targeted liposomes have the ability to escape endosomes to enter the mitochondria.

Figure 9

Mitochondria targeting polymer from PCL-PEG modified with a linker containing TPP between PCL and PEG. Drawn based on Reference (109).

Figure 10

Precise engineering of polymeric NPs to control NP size and surface charge for effective mitochondria targeting properties (top) and mitochondrial localization targeted-NPs and cytosolic distribution of non-targeted NPs (bottom). Redrawn using original data from Reference .

Figure 11

Mitochondria targeted NP system based on PLGA-b-PEG-TPP for entrapment of various mitochondria acting therapeutics. Redrawn based on Reference (79).

Figure 12

Mitochondria targeted NPs for PDT localized to mitochondria and mechanism of action for light triggered immune activation. Redrawn based on Reference (106)