Facile Synthesis of Monodispersed Mesoporous Silica Nanoparticles with Ultralarge Pores and Their Application in Gene Delivery

Kim, Mi-Hee; Na, Hee-Kyung; Kim, Young‐Kwan; Ryoo, Soo‐Ryoon; Cho, Hae Sung; Lee, Jun Young; Jeon, Hyesung; Ryoo, Ryong; Min, Dal‐Hee

doi:10.1021/nn103130q

Cited by 340 publications

(246 citation statements)

References 34 publications

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“…1 and Supplementary Note 1) were developed as a proteasome transporter. MSNPN were synthesized to have pore sizes between 25 and 30 nm using a pore expansion strategy 12,13 , which can harbour a proteasome holoenzyme molecule through noncovalent interactions with the polyhistidine (His) tag of proteasomes (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

Direct cellular delivery of human proteasomes to delay tau aggregation

Han

Choi

et al. 2014

Nat Commun

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The 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been suggested that the elevation of proteasomal activity is tolerable to cells and may be beneficial to prevent the accumulation of protein aggregates. Here we show that purified proteasomes can be directly transported into cells through mesoporous silica nanoparticle-mediated endocytosis. Proteasomes that are loaded onto nanoparticles through non-covalent interactions between polyhistidine tags and nickel ions fully retain their proteolytic activity. Cells treated with exogenous proteasomes are more efficient in degrading overexpressed human tau than endogenous proteasomal substrates, resulting in decreased levels of tau aggregates. Moreover, exogenous proteasome delivery significantly promotes cell survival against proteotoxic stress caused by tau and reactive oxygen species. These data demonstrate that increasing cellular proteasome activity through the direct delivery of purified proteasomes may be an effective strategy for reducing cellular levels of proteotoxic proteins.

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Section: Resultsmentioning

confidence: 99%

Direct cellular delivery of human proteasomes to delay tau aggregation

Han

Choi

et al. 2014

Nat Commun

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“…15,18 Second, nanosize particles lead to higher cellular uptake compared to the micrometer size particles. 4,16 From these results, we see the potency of using large pore mesoporous silica nanoparticles (LP-MSNs) as carriers for siRNA delivery. However, the successful application of LP-MSNs for delivery of nucleic acidbased drugs requires surface modification of the silica in order to generate sufficient binding affinity for the negatively charged nucleic acids.…”

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confidence: 95%

Poly-l-lysine Functionalized Large Pore Cubic Mesostructured Silica Nanoparticles as Biocompatible Carriers for Gene Delivery

et al. 2012

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Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-l-lysine (PLL) were designed as a new carrier material for gene delivery applications. The synthesized LP-MSNs are 100–200 nm in diameter and are composed of cage-like pores organized in a cubic mesostructure. The size of the cavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto the silica surface through covalent immobilization was confirmed by X-ray photoelectron spectroscopy, solid-state 13C magic-angle spinning nuclear magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis. As a result of the particle modification with PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs was observed compared to the native unmodified silica particles. Consequently, PLL-functionalized nanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as gene carriers compared to amino-functionalized nanoparticles and the native nanoparticles. The system was tested to deliver functional siRNA against minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated great potential for efficient gene transfer into cancer cells as a decrease of the cellular viability of the osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles also exhibit a high biocompatibility, with low cytotoxicity observed up to 100 μg/mL.

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“…Following this premise, the group of Min compared the loading and release behaviour of both MSNs (2.1 nm) and LP-MSNs (23 nm) functionalized with amino groups. 107,108 They suggested that large-pore particles were able to host nucleic acids into their structure while regular-pore MSNs could only adsorb them at the surface. To demonstrate this, the authors loaded the corresponding nanoparticles with either the GFP plasmid DNA 107 or its opposite the GFP siRNA 108 and submitted both materials to a nuclease enzymatic prior to an in vitro testing.…”

Section: Loading Nucleotides Into Msns: New Devices For Transfection mentioning

confidence: 99%

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

Castillo¹,

Baeza²

2017

Biomater. Sci.

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The discovery and control of the biological roles mediated by nucleic acids have turned them into a powerful tool for the development of advanced biotechnological materials. Much is the importance of those gene-keeping biomacromolecules that even nanomaterials have succumbed to the claimed benefits of DNA and RNA. Currently, there could be found in the literature a practically intractable number of examples which report the use in combination of nanoparticles with nucleic acids, which demands boundedness. Following this premise, this revision will only cover the most recent and powerful strategies developed to exploit the possibilities of nucleic acids as biotechnological materials when in combination with mesoporous silica nanoparticles. The extensive research done on nucleic acids has significantly incremented the technological possibilities for those biomacromolecules, which could be employed in many different applications; where substrate or sequence recognition or modulation of biological pathways due to its coding role in living cells are the most promising. In the present revision, the chosen counterpart, mesoporous silica nanoparticles, also with unique properties, became a reference material for drug delivery and biomedical applications due to their high biocompatibility and porous structure suitable for hosting and delivering small molecules. Although most of revisions deal with significant advances in the use of nucleic acid and mesoporous silica nanoparticles in biotechnological applications, a rationale classification of those new generation hybrid materials is still uncovered. Along this review there will be covered promising strategies for living cell and biological sensors, DNA-based molecular gates with targeting, transfection or silencing properties which could provide a significant advance of current nanomedicine.

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Facile Synthesis of Monodispersed Mesoporous Silica Nanoparticles with Ultralarge Pores and Their Application in Gene Delivery

Cited by 340 publications

References 34 publications

Direct cellular delivery of human proteasomes to delay tau aggregation

Direct cellular delivery of human proteasomes to delay tau aggregation

Poly-l-lysine Functionalized Large Pore Cubic Mesostructured Silica Nanoparticles as Biocompatible Carriers for Gene Delivery

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

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