Functionalized nanosystems for targeted mitochondrial delivery

Durazo, Shelley A.; Kompella, Uday B.

doi:10.1016/j.mito.2011.11.001

Cited by 68 publications

(41 citation statements)

References 82 publications

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“…Based on the mitochondrial membrane features, physicochemical properties of NPs have been well characterized. 63 Outer mitochondrial membrane can permeate NPs up to 3 nm in size and molecules with a molecular weight less than 5000 daltons through voltage-dependent anion channels. If the therapeutic target is within the mitochondrial matrix, the drug will also have to cross the inner membrane, which has a strong negative potential, thus drug lipophilicity, charge, and polar surface area positively influence the delivery that may be achieved also by integrating mitochondrial translocation ligands and/ or positively charged ligands into the NP design.…”

Section: Specific Intracellular Nanoparticle Targetingmentioning

confidence: 99%

The effect of nanoparticle uptake on cellular behavior: disrupting or enabling functions?

Panariti¹,

Miserocchi²,

Rivolta³

2012

NSA

171

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Nanoparticles (NPs) are materials with overall dimensions in the nanoscale range. They have unique physicochemical properties, and have emerged as important players in current research in modern medicine. In the last few decades, several types of NPs and microparticles have been synthesized and proposed for use as contrast agents for diagnostics and imaging and for drug delivery; for example, in cancer therapy. Yet specific targeting that will improve their delivery still represents an unsolved challenge. The mechanism by which NPs enter the cell has important implications not only for their fate but also for their impact on biological systems. Several papers in the literature discuss the potential risks related to NP exposure, and more recently the concept that even sublethal doses of NPs may elicit a cell response has been proposed. In this review, we intend to present an overall view of cell mechanisms that may be perturbed by cell-NP interaction. Published data, in fact, emphasize that NPs should no longer be viewed only as simple carriers for biomedical applications, but that they can also play an active role in mediating biological effects.

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Section: Specific Intracellular Nanoparticle Targetingmentioning

confidence: 99%

The effect of nanoparticle uptake on cellular behavior: disrupting or enabling functions?

Panariti¹,

Miserocchi²,

Rivolta³

2012

NSA

171

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“…1,5 As a consequence, mitochondrial dysfunction has been linked to a range of diseases in these tissues (and others) including neurodegenerative and neuromuscular disorders, cancer, ischemiareperfusion injury, metabolic diseases such as diabetes and obesity, chronic autoimmune inflammatory diseases, kidney and liver diseases, and aging. 1,3,[6][7][8][9][10] In spite of the clinical relevance of these mitochondrial-related diseases many still lack effective therapeutic options. 1,11 The ability to design mitochondrial-targeting systems may therefore provide valuable alternative strategies to enhance therapeutic outcomes of mitochondrial-related diseases while at the same time minimizing side effects associated with the therapeutic molecules.…”

Section: Introductionmentioning

confidence: 99%

Effect of the Conjugation Density of Triphenylphosphonium Cation on the Mitochondrial Targeting of Poly(amidoamine) Dendrimers

et al. 2015

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Many clinically relevant diseases with known poor therapeutic outcomes, including cancer and neurodegenerative disorders, have been directly linked to mitochondrial dysfunction. The ability to efficiently target therapeutics to intracellular organelles such as mitochondria may represent new opportunities for the effective treatment of such ailments. The present study reports the synthesis, cellular uptake, cytotoxicity, and mitochondrial colocalization of conjugates of triphenylphosphonium cation (TPP) to amine-terminated, generation 4, poly(amidoamine) (PAMAM) dendrimer (G4NH2) nanocarriers. The mitochondrial-targeting moiety TPP was either directly conjugated to G4NH2 (G4NH2-TPP) or to the dendrimer through a flexible polyethylene glycol (PEG) linker (G4NH2-PEGTPP). Conjugation was done at various TPP densities to assess their biological activity and potential for mitochondrial-targeted drug delivery. Tests in an in vitro model of the human alveolar carcinoma (A549 cells) showed that even at a low TPP density (∼5 TPP) both the cellular internalization and mitochondrial targeting increase significantly, as determined by fluorescence activated cell sorting (FACS) and confocal microscopy (CM), respectively. At a density of ∼10 TPP per G4NH2, further increase in cellular internalization and mitochondrial targeting was achieved. However, at this higher density, the nanocarriers also showed pronounced cytotoxicity. It was observed that the toxicity of the conjugates is decreased upon the addition of a PEG linker between the dendrimer and TPP (G4NH2-PEGTPP), while the mitochondrial targeting ability of the nanocarriers is not affected as the PEG density increases. The proposed strategies indicate that TPP-conjugated G4NH2 dendrimers represent a potentially viable strategy for the targeting of therapeutic molecules to mitochondria, which may help improve therapeutic outcomes of diseases related to mitochondrial dysfunction.

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“…154 Thus far, most studies have primarily developed metal oxide or liposomal NPs for delivery to the mitochondria. Delivery to the mitochondria has also been based on electrostatic interactions between the NP and the organelle.…”

Section: Nanoparticle Applications In Biologymentioning

confidence: 99%

Nanoparticles and their applications in cell and molecular biology

Wang

2013

Integrative Biology

356

138

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Nanoparticles can be engineered with distinctive compositions, sizes, shapes, and surface chemistries to enable novel techniques in a wide range of biological applications. The unique properties of nanoparticles and their behavior in biological milieu also enable exciting and integrative approaches to studying fundamental biological questions. This review will provide an overview of various types of nanoparticles and concepts of targeting nanoparticles. We will also discuss the advantages and recent applications of using nanoparticles as tools for drug delivery, imaging, sensing, and for the understanding of basic biological processes.

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Functionalized nanosystems for targeted mitochondrial delivery

Cited by 68 publications

References 82 publications

The effect of nanoparticle uptake on cellular behavior: disrupting or enabling functions?

The effect of nanoparticle uptake on cellular behavior: disrupting or enabling functions?

Effect of the Conjugation Density of Triphenylphosphonium Cation on the Mitochondrial Targeting of Poly(amidoamine) Dendrimers

Nanoparticles and their applications in cell and molecular biology

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