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Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio.

Nomani A, Haririan I, Rahimnia R, Fouladdel S, Gazori T, Dinarvand R, Omidi Y, Azizi E - Int J Nanomedicine (2010)

Bottom Line: PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer.For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5'-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture.This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT
To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5'-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity.

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Size distribution by intensity of PAMAM/ANS nanoparticles (a and b) and Zeta potential graphs of different N/P ratios of PAMAM G3 (), G4 (), and G5 (▪) in 5% dextrose (c). Fixed concentrations of 500 nM of ANS in 5% dextrose were mixed with different generations of PAMAM at N/P ratio of 10 a). Part a) shows all size distributions at the same intensity scale in one graph. A peak of larger aggregates of G2/ANS nanoparticles can be observed in part a). Nanoparticles of various N/P ratios of PAMAM G5 which were formulated in 5% dextrose are shown in part b). In part c), the represented data are means of two (without error bar) or three (mean ± SD) measurements.Abbreviations: PAMAM, poly(amidoamine) dendrimer; SD, standard deviation; ANS, antisense oligonucleotide.
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f1-ijn-5-359: Size distribution by intensity of PAMAM/ANS nanoparticles (a and b) and Zeta potential graphs of different N/P ratios of PAMAM G3 (), G4 (), and G5 (▪) in 5% dextrose (c). Fixed concentrations of 500 nM of ANS in 5% dextrose were mixed with different generations of PAMAM at N/P ratio of 10 a). Part a) shows all size distributions at the same intensity scale in one graph. A peak of larger aggregates of G2/ANS nanoparticles can be observed in part a). Nanoparticles of various N/P ratios of PAMAM G5 which were formulated in 5% dextrose are shown in part b). In part c), the represented data are means of two (without error bar) or three (mean ± SD) measurements.Abbreviations: PAMAM, poly(amidoamine) dendrimer; SD, standard deviation; ANS, antisense oligonucleotide.

Mentions: Self-assembled nanoparticles of the G2 through G4 of PAMAM with ANS at N/P ratio of 10 had a peak between the ranges of 40–500 nm. For G5 at different N/P ratios a peak in the range of 40–1100 nm was repeatable (Figures 1a, 1b and Table 1). The higher the N/P ratio, the narrower the observed particle distribution (Table 1). For example, for generation 5 the particles larger than 800 nm, present at the N/P ratio of 0.5 were not observed at higher N/P ratios (Figure 1b and Table 1). In some cases, especially for the lower generations, the graph was multimodal instead of a single peak. Various repeats of the measurements revealed that by increasing the charge ratios, the probability of observing multiple peaks decreased.


Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio.

Nomani A, Haririan I, Rahimnia R, Fouladdel S, Gazori T, Dinarvand R, Omidi Y, Azizi E - Int J Nanomedicine (2010)

Size distribution by intensity of PAMAM/ANS nanoparticles (a and b) and Zeta potential graphs of different N/P ratios of PAMAM G3 (), G4 (), and G5 (▪) in 5% dextrose (c). Fixed concentrations of 500 nM of ANS in 5% dextrose were mixed with different generations of PAMAM at N/P ratio of 10 a). Part a) shows all size distributions at the same intensity scale in one graph. A peak of larger aggregates of G2/ANS nanoparticles can be observed in part a). Nanoparticles of various N/P ratios of PAMAM G5 which were formulated in 5% dextrose are shown in part b). In part c), the represented data are means of two (without error bar) or three (mean ± SD) measurements.Abbreviations: PAMAM, poly(amidoamine) dendrimer; SD, standard deviation; ANS, antisense oligonucleotide.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2875730&req=5

f1-ijn-5-359: Size distribution by intensity of PAMAM/ANS nanoparticles (a and b) and Zeta potential graphs of different N/P ratios of PAMAM G3 (), G4 (), and G5 (▪) in 5% dextrose (c). Fixed concentrations of 500 nM of ANS in 5% dextrose were mixed with different generations of PAMAM at N/P ratio of 10 a). Part a) shows all size distributions at the same intensity scale in one graph. A peak of larger aggregates of G2/ANS nanoparticles can be observed in part a). Nanoparticles of various N/P ratios of PAMAM G5 which were formulated in 5% dextrose are shown in part b). In part c), the represented data are means of two (without error bar) or three (mean ± SD) measurements.Abbreviations: PAMAM, poly(amidoamine) dendrimer; SD, standard deviation; ANS, antisense oligonucleotide.
Mentions: Self-assembled nanoparticles of the G2 through G4 of PAMAM with ANS at N/P ratio of 10 had a peak between the ranges of 40–500 nm. For G5 at different N/P ratios a peak in the range of 40–1100 nm was repeatable (Figures 1a, 1b and Table 1). The higher the N/P ratio, the narrower the observed particle distribution (Table 1). For example, for generation 5 the particles larger than 800 nm, present at the N/P ratio of 0.5 were not observed at higher N/P ratios (Figure 1b and Table 1). In some cases, especially for the lower generations, the graph was multimodal instead of a single peak. Various repeats of the measurements revealed that by increasing the charge ratios, the probability of observing multiple peaks decreased.

Bottom Line: PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer.For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5'-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture.This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT
To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5'-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was dependent upon the generation and charge ratio of the PAMAM dendrimer, and the antisense concentration had no significant effect on the cytotoxicity.

Show MeSH
Related in: MedlinePlus