Synthesis of acridine-nuclear localization signal (NLS) conjugates and evaluation of their impact on lipoplex and polyplex-based transfection

Boulanger, Caroline; Giorgio, Christophe Di; Vierling, Pierre

doi:10.1016/j.ejmech.2005.07.015

Cited by 44 publications

(37 citation statements)

References 25 publications

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“…The photoluminescent NPs were clearly observed accumulating in the cytoplasm and the nucleus of HeLa cells [116]. Intracellular delivery of liposome-carrying plasmid DNA has also been reported by a number of groups using nuclear localization signal peptides derived from various sources including SV40 virus [119] and the amino terminal region of the polyoma virus [120].…”

Section: Delivery Of Therapeutic Proteinsmentioning

confidence: 89%

Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing nanoparticle-mediated Drug Delivery

Delehanty¹,

Boeneman

Bradburne

et al. 2010

Therapeutic Delivery

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The use of peptides to mediate the delivery and uptake of nanoparticle (NP) materials by mammalian cells has grown significantly over the past 10 years. This area of research has important implications for the development of new therapeutic materials and for the emerging field of NP-mediated drug delivery. In this review, we highlight recent advances in the delivery of various NPs by some of the more commonly employed cellular delivery peptides and discuss important related factors such as NP-peptide bioconjugation, uptake efficiency, intracellular fate and toxicity. We also highlight various demonstrations of therapeutic applications of NP-peptide conjugates where appropriate. The paper concludes with a brief forward-looking perspective discussing what can be expected as this field develops in the coming years.

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Section: Delivery Of Therapeutic Proteinsmentioning

confidence: 89%

Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing nanoparticle-mediated Drug Delivery

Delehanty¹,

Boeneman

Bradburne

et al. 2010

Therapeutic Delivery

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“…7 Other coupling reagents as EDC·HCl, DIPCDI, TFFH, PyBOP with HOAt, and MSNT with NMI failed in ester bond formation. 8 Compound 3 quickly hydrolyzes and liberates Lam-D into the medium, even on the time scale of an HPLC analysis. …”

Section: Esterification and Synthesis Of Conjugates 1-4mentioning

confidence: 99%

Lamellarin D Bioconjugates II: Synthesis and Cellular Internalization of Dendrimer and Nuclear Location Signal Derivatives

et al. 2009

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BarcelonaRECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to) TITLE RUNNING HEAD. Lamellarin D -NLS and DTPA conjugates.ABSTRACT: The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4 to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines (MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3, 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed and nuclear distribution pattern was observed for 4, which contains a nuclear localization signalling sequence.

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“…Fusion proteins containing a NLS have been widely used to exploit intracellular transport mechanisms and promote the translocation of macromolecules into the cell nucleus. We can also find many examples of the use of the NLS peptides conjugated to different compounds to enhance their cytotoxicity [15][16][17]. In this work, we have investigated the relationship between the cytotoxicity produced by PE5 and its ability to reach the nucleus and degrade nuclear RNA.…”

Section: Introductionmentioning

confidence: 99%

The nuclear transport capacity of a human-pancreatic ribonuclease variant is critical for its cytotoxicity

et al. 2010

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We have previously described a human pancreatic-ribonuclease variant, named PE5, which carries a non-contiguous extended bipartite nuclear localization signal. This signal comprises residues from at least three regions of the protein. We postulated that the introduction of this signal in the ribonuclease provides it with cytotoxic activity because although the variant poorly evades the ribonuclease inhibitor in vitro, it is routed to the nucleus, which is devoid of the inhibitor. In this work, we have investigated the relationship between the cytotoxicity produced by PE5 and its ability to reach the nucleus. First, we show that this enzyme, when incubated with HeLa cells, specifically cleaves nuclear RNA while it leaves cytoplasmic RNA unaffected. On the other hand, we have created new variants in which the residues of the nuclear localization signal that are important for the nuclear transport have been replaced. As expected, the individual changes produce a significant decrease in the cytotoxicity of the resulting variants. We conclude that the nuclear transport of PE5 is critical for its cytotoxicity. Therefore, routing a ribonuclease to the nucleus is an alternative strategy to endow it with cytotoxic activity.

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Synthesis of acridine-nuclear localization signal (NLS) conjugates and evaluation of their impact on lipoplex and polyplex-based transfection

Cited by 44 publications

References 25 publications

Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing nanoparticle-mediated Drug Delivery

Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing nanoparticle-mediated Drug Delivery

Lamellarin D Bioconjugates II: Synthesis and Cellular Internalization of Dendrimer and Nuclear Location Signal Derivatives

The nuclear transport capacity of a human-pancreatic ribonuclease variant is critical for its cytotoxicity

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