A Cationic Derivative of Amphotericin B as a Novel Delivery System for Antisense Oligonucleotides

Garcia-Chaumont, Christine; Seksek, Olivier; Jollès, Béatrice; Bolard, Jacques

doi:10.1089/oli.1.2000.10.177

Cited by 14 publications

(7 citation statements)

References 49 publications

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“…Current strategies to reverse MDR are based: (i) on the synthesis of new non‐cross resistant cytostatics (Antonini et al ., 1995; Bassan et al ., 1997; Kubota et al ., 1998; Stefańska et al ., 1999); (ii) on the identification of effective and more selective MDR reversing agents (chemosensitizers) (Raderer & Scheithaner, 1993; Pereira et al ., 1994; Mankhetkorn & Garnier‐Suillerot, 1996; Pascaud et al ., 1998; Berger et al ., 1999; Teodori et al ., 1999); (iii) on the selective inhibition of gene expression encoding ATP‐dependent export pump using antisense oligonucleotides (Alahari et al ., 1996; Stewart et al ., 1996; Garcia‐Chaumont et al ., 2000) or ribozymes (Palfner et al ., 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Current strategies to reverse MDR are based: (i) on the synthesis of new non-cross resistant cytostatics (Antonini et al, 1995;Bassan et al, 1997;Kubota et al, 1998;StefanÂ ska et al, 1999); (ii) on the identi®cation of eective and more selective MDR reversing agents (chemosensitizers) (Raderer 1996;Garcia-Chaumont et al, 2000) or ribozymes (Palfner et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Anthrapyridones, a novel group of antitumour non‐cross resistant anthraquinone analogues. Synthesis and molecular basis of the cytotoxic activity towards K562/DOX cells

Tarasiuk

Stefańska

Plodzich

et al. 2002

British J Pharmacology

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1 Multidrug resistance (MDR) to antitumour agents, structurally dissimilar and having di erent intracellular targets, is the major problem in cancer therapy. MDR phenomenon is associated with the presence of membrane proteins which belong to the ATP-binding cassette family transporters responsible for the active drug e ux leading to the decreased intracellular accumulation. 2 The search of new compounds able to overcome MDR is of prime importance. 3 Recently we have synthesized a new family of anthrapyridone compounds. The series contained derivatives modi®ed with appropriate hydrophobic or hydrophylic substituents at the side chain. 4 The interaction of these derivatives with erythroleukemia K562 sensitive and K562/DOX resistant (overexpressing P-glycoprotein) cell lines has been examined. The study was performed using a spectro¯uorometric method which allows to continuously follow the uptake and e ux of uorescent molecules by living cells. 5 It was demonstrated that the increase in the lipophilicity of anthrapyridones favoured the very fast cellular uptake exceeding the rate of P-gp dependent e ux out of the cell. For these derivatives, very high accumulation (the same for sensitive and resistant cells) was observed and the in vitro biological data con®rmed that these compounds exhibited comparable cytotoxic activity towards sensitive and P-gp resistant cell line. In contrast, anthrapyridones modi®ed with hydrophylic substituents exhibited relatively low kinetics of cellular uptake. 6 For these derivatives decreased accumulation in resistant cells was observed and the in vitro biological data demonstrated that they were much less active against P-gp resistant cells in comparison to sensitive cells. 7 We also studied, using confocal microscopy, the intracellular distribution of anthrapyridones in NIH-3T3 cells. Our data showed that these compounds were strongly accumulated in the nucleus and lysosomes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anthrapyridones, a novel group of antitumour non‐cross resistant anthraquinone analogues. Synthesis and molecular basis of the cytotoxic activity towards K562/DOX cells

Tarasiuk

Stefańska

Plodzich

et al. 2002

British J Pharmacology

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“…AmA, a polyene antibiotic and a promising cationic vector, brings new possibilities toward efficient and suitable transport and following distribution of the modified oligonucleotide 13. B16 cells incubated with the mixture TMR‐dT 15 /AmA exhibit significantly enhanced intracellular oligonucleotide uptake.…”

Section: Resultsmentioning

confidence: 99%

Intracellular uptake of modified oligonucleotide studied by two fluorescence techniques

et al. 2004

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Interaction, i.e., cellular uptake and intracellular distribution, of synthetic modified antisense oligonucleotide with the B16 melanoma cell line was studied using cationic polyene antibiotic, amphotericin B 3-dimethylaminopropyl amide, as a carrier vector. The antisense oligonucleotide--dT(15) oligomer analogue containing isopolar, nonisosteric, phosphonate-based internucleotide linkages 3'-O-P-CH(2)-O-5'--was labeled with fluorescent tetramethylrhodamine marker. The oligonucleotide itinerancy across the cell membrane and its distribution inside the cell was visualized using fluorescence microimaging. During the first several hours a strong preference staining of the cell nucleus was found. Fluorescence lifetime measurements from the intracellular environment (confocal laser microspectrofluorimeter, frequency domain phase/modulation technique in 1 to 200 MHz frequency region) yielded two spectral components of 4.9 and 1.4 ns lifetime, respectively. While the former component correlates with the previously characterized effect of the fluorophore binding to biomolecular targets in membranes and/or cytoplasm, the latter component is newly observed and its possible origin is discussed.

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“…In this experiments a 42 mer antisense against human APP. Amphotericin B was first used by us to transport DNA (Kumar et al, 1974) and later shown to be a valuable agent for the transport of oligonucleotides into 3T3 cells (Garcia-Chaumont et al, 2000). Using CaCl 2 or Amphotericin B would cause some cell death if we cross concentrations above 1mM and 10 µM respectively.…”

Section: Uptake Of Antisense Oligonucleotidesmentioning

confidence: 99%

Recent Developments in Molecular Changes Leading to Alzheimer’s Disease and Novel Therapeutic Approaches

Kumar¹

2011

Advanced Understanding of Neurodegenerative Diseases

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A Cationic Derivative of Amphotericin B as a Novel Delivery System for Antisense Oligonucleotides

Cited by 14 publications

References 49 publications

Anthrapyridones, a novel group of antitumour non‐cross resistant anthraquinone analogues. Synthesis and molecular basis of the cytotoxic activity towards K562/DOX cells

Anthrapyridones, a novel group of antitumour non‐cross resistant anthraquinone analogues. Synthesis and molecular basis of the cytotoxic activity towards K562/DOX cells

Intracellular uptake of modified oligonucleotide studied by two fluorescence techniques

Recent Developments in Molecular Changes Leading to Alzheimer’s Disease and Novel Therapeutic Approaches

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