| Title |
Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro
|
|---|---|
| Published in |
International Journal of Nanomedicine, September 2015
|
| DOI | 10.2147/ijn.s87307 |
| Pubmed ID | |
| Authors |
Łukasz Uram, Magdalena Szuster, Aleksandra Filipowicz, Krzysztof Gargasz, Stanisław Wołowiec, Elżbieta Wałajtys-Rode |
| Abstract |
The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin-pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander's coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%-35% of the total nuclei area at all investigated concentrations, with lower level (15%-25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%-20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 25% |
| Unknown | 3 | 75% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 3 | 75% |
| Members of the public | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 27% |
| Student > Bachelor | 3 | 14% |
| Student > Master | 3 | 14% |
| Researcher | 3 | 14% |
| Student > Doctoral Student | 2 | 9% |
| Other | 2 | 9% |
| Unknown | 3 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 4 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 14% |
| Neuroscience | 3 | 14% |
| Biochemistry, Genetics and Molecular Biology | 2 | 9% |
| Medicine and Dentistry | 2 | 9% |
| Other | 3 | 14% |
| Unknown | 5 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 September 2015.
All research outputs
#15,738,224
of 25,371,288 outputs
Outputs from International Journal of Nanomedicine
#1,775
of 4,121 outputs
Outputs of similar age
#142,281
of 276,785 outputs
Outputs of similar age from International Journal of Nanomedicine
#61
of 154 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,121 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 54% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 276,785 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 154 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.