Cell-penetrating CNTs for delivery of therapeutics

Lacerda, Lara; Raffa, Vittoria; Prato, Maurizio; Bianco, Alberto; Kostarelos, Kostas

doi:10.1016/s1748-0132(07)70172-x

Cited by 227 publications

(129 citation statements)

References 29 publications

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“…So far, besides the demonstration of the ability of CNTs to enter and penetrate cell membranes [1][2][3][4], the uptake mechanism is still debated and may involve more than one process. Indeed, Kam et al and Jin et al .…”

Section: Introductionmentioning

confidence: 99%

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

et al. 2012

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The carbon nanotubes (CNT) complexes (RNA-wrapped, oxidized DWNT) were endocytosed by capture in clathrin-coated vesicles, revealed by clear co-localization with both clathrin and transferrin. CNT complexes were also found in early endosomes, which was confirmed by co-localization with early endosome antigen (EEA). CNT complexes were not sorted for recycling back to the cell membrane (via fast recycling endosomes), as co-localization with Rab 4 was not observed.Instead, the overlapping of CNT complexes with both LAMP2 antibody and LysoTracker® marker indicated their sequestration in lysosomes.CNTs were also found within within vesicles of the secretory pathway (Rab11-positive vesicles), which for the first time suggests an exact route for their exocytosis. ABSTRACTCarbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT-RNA) is presented. Fixed cells, previously exposed to oxDWNT-RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT-RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT-RNA with the small GTP-binding protein (Rab11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network.

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Section: Introductionmentioning

confidence: 99%

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

et al. 2012

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“…f -CNT possess unique features that make them extremely attractive for the construction of unique gene delivery vectors. Most importantly, f -CNT have the ability to interact with biological components and be internalized efficiently in different cell types by different mechanisms (20)(21)(22). Several studies have shown promising results, exploiting f -CNT characteristics for pDNA and siRNA delivery in vitro and in vivo (17,18,20,(23)(24)(25)(26)(27)(28).…”

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confidence: 99%

Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing

Al‐Jamal

Gherardini

Bardi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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218

122

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Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.nanomedicine | neurodegenerative | neuroprotection | neurosciences | gene therapy

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“…The needle-like structure of nanotubes allows for advanced medical applications. For example, the ability of nanotubes to translocate through plasma membranes allows their use for the delivery of therapeutically active molecules in a manner that resembles cell-penetrating peptides [176]. Prato et al [177] describe how nanotubes open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today, with the additional advantage that adequately functionalized CNTs can be rapidly eliminated from the body [177].…”

Section: Drug Deliverymentioning

confidence: 99%

The Separation Power of Nanotubes in Membranes: A Review

Bruggen

2012

ISRN Nanotechnology

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Research on mixed matrix membranes in which nanoparticles are used to enhance the membrane's performance in terms of flux, separation, and fouling resistance has boomed in the last years. This review probes on the specific features and benefits of one specific type of nanoparticles with a well-defined cylindrical structure, known as nanotubes. Nanotube structures for potential use in membranes are reviewed. These comprise mainly single-wall carbon nanotubes (SWCNTs) and multiwall carbon nanotubes (MWCNTs), but also other structures and materials, which are less studied for membrane applications, can be used. Important issues related to polymer-nanotube interactions such as dispersion and alignment are outlined, and a categorization is made of the resultant membranes. Applications are reviewed in four different areas, that is, gas separation, water filtration, drug delivery, and fuel cells.

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Cell-penetrating CNTs for delivery of therapeutics

Cited by 227 publications

References 29 publications

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing

The Separation Power of Nanotubes in Membranes: A Review

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