Development of a nanoparticle that releases nucleic acids in response to a mitochondrial environment

Yamada, Yuma; Fukuda, Yutaka; Sasaki, Daisuke; Maruyama, Minako; Harashima, Hideyoshi

doi:10.1016/j.mito.2020.02.009

Cited by 16 publications

(12 citation statements)

References 33 publications

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“…For example, the nuclear membrane is a barrier for genome editing or DNA delivery 75,149 . NPs targeting the mitochondria for specific cancers or as neurogenerative or cardiovascular therapies face similar barriers 75,182 ; to overcome this challenge, pH-responsive NP systems could aid in precise delivery to the mitochondrial environment 183 .…”

Section: Cellular and Intracellular Barriersmentioning

confidence: 99%

“…Delivery of genome-editing systems is challenging because these systems are multicomponent, hold sensitive cargo and need to overcome several extracellular and intracellular biological barriers to reach the genome of target cells. Lipid-based and polymer-based NPs have delivered a range of nucleic acids in vivo, and are in various stages of clinical development 24,44,104,183 . For example, a LNP siRNA drug termed Onpattro (patisiran) was recently approved by the FDA for the treatment of amyloidosis 270 .…”

Section: Nps For Genome Editingmentioning

confidence: 99%

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Engineering precision nanoparticles for drug delivery

Mitchell

Billingsley

Haley

et al. 2020

Nat Rev Drug Discov

4,510

2,814

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In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

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Section: Cellular and Intracellular Barriersmentioning

confidence: 99%

Section: Nps For Genome Editingmentioning

confidence: 99%

Engineering precision nanoparticles for drug delivery

Mitchell

Billingsley

Haley

et al. 2020

Nat Rev Drug Discov

4,510

2,814

View full text Add to dashboard Cite

show abstract

“…We previously developed a MITO-Porter 3-8 a liposomal DDS for delivering cargoes to mitochondria, and reported that such a MITO-Porter system successfully delivered various cargoes including lowmolecular-weight compounds (e.g., anti-cancer drugs, 9 a porphyrintype chemical, 10 coenzyme Q 10 11 ) and macromolecules such as nucleic acids [12][13][14][15] to mitochondria via mitochondrial membrane fusion. We assumed that the MITO-Porter system could accelerate the cellular uptake of vitamin B 1 and would eventually reach the mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Validation of the Mitochondrial Delivery of Vitamin B1 to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast

Yamada

Ishimaru

Ikeda

et al. 2022

Journal of Pharmaceutical Sciences

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“…Moreover, they can be functionalized with different macromolecules, including polymers, peptides, antibodies, and even nucleic acids [ 12 , 13 ]. For instance, the obtained nanoconjugates have found applications in the ultrasensitive detection of biological species or the targeted delivery of nucleic acids at the subcellular level [ 14 , 15 ]. Most patchy core/shell nanoparticles’ synthesis methods mainly rely on bottom–up approaches where chemical precursors can self-assemble into the desired arrangement in multi-stage processes with controlled conditions [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Patchy Core/Shell, Magnetite/Silver Nanoparticles via Green and Facile Synthesis: Routes to Assure Biocompatibility

et al. 2020

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Nanomedicine is entering a high maturity stage and is ready to reach full translation into the clinical practice. This is because of the ample spectrum of applications enabled by a large arsenal of nanostructured materials. In particular, bimetallic patchy core/shell nanoparticles offer tunable surfaces that allow multifunctional responses. Despite their attractiveness, major challenges regarding the environmental impact and biocompatibility of the obtained materials are yet to be solved. Here, we developed a green synthesis scheme to prepare highly biocompatible patchy core/shell magnetite/silver nanoparticles for biological and biomedical applications. The magnetite core was synthesized by the co-precipitation of ferric chloride and ferrous chloride in the presence of NaOH. This was followed by the patchy silver shell’s growth by a green synthesis approach based on natural honey as a reducing agent. A purification process allowed selecting the target patchy nanoparticles and removing excess toxic reagents from the synthesis very efficiently. The obtained patchy magnetite/silver nanoparticles were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope equipped with energy-dispersive spectroscopy (SEM + EDS), and transmission electron microscopy (TEM). The morphology, patchiness level, and size of the nanoparticles were determined via SEM and TEM. In addition, the spectrophotometric characterization confirmed the presence of the patchy silver coating on the surface of the magnetite core. The nanoparticles show high biocompatibility, as evidenced by low cytotoxicity, hemolytic effect, and platelet aggregation tendency. Our study also provides details for the conjugation of multiples chemistries on the surface of the patchy bimetallic nanoparticles, which might be useful for emerging applications in nanomedicine, where high biocompatibility is of the utmost importance.

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Development of a nanoparticle that releases nucleic acids in response to a mitochondrial environment

Cited by 16 publications

References 33 publications

Engineering precision nanoparticles for drug delivery

Engineering precision nanoparticles for drug delivery

Validation of the Mitochondrial Delivery of Vitamin B1 to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast

Patchy Core/Shell, Magnetite/Silver Nanoparticles via Green and Facile Synthesis: Routes to Assure Biocompatibility

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