| Title |
Trastuzumab- and Fab′ fragment-modified curcumin PEG-PLGA nanoparticles: preparation and evaluation in vitro and in vivo
|
|---|---|
| Published in |
International Journal of Nanomedicine, March 2018
|
| DOI | 10.2147/ijn.s153795 |
| Pubmed ID | |
| Authors |
Dongyu Duan, Aiping Wang, Ling Ni, Liping Zhang, Xiuju Yan, Ying Jiang, Hongjie Mu, Zimei Wu, Kaoxiang Sun, Youxin Li |
| Abstract |
Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab' (antigen-binding fragments cut from TMAB)-modified NPs (Fab'-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells. The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs. Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery. |
Mendeley readers
The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 70 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 16 | 23% |
| Student > Ph. D. Student | 13 | 19% |
| Researcher | 4 | 6% |
| Student > Doctoral Student | 3 | 4% |
| Student > Bachelor | 3 | 4% |
| Other | 9 | 13% |
| Unknown | 22 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 17 | 24% |
| Chemistry | 8 | 11% |
| Biochemistry, Genetics and Molecular Biology | 5 | 7% |
| Engineering | 3 | 4% |
| Agricultural and Biological Sciences | 3 | 4% |
| Other | 11 | 16% |
| Unknown | 23 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 03 April 2018.
All research outputs
#6,354,972
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#639
of 4,122 outputs
Outputs of similar age
#103,267
of 344,853 outputs
Outputs of similar age from International Journal of Nanomedicine
#8
of 81 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 4,122 research outputs from this source. They receive a mean Attention Score of 4.7. This one has done well, scoring higher than 84% 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 344,853 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 81 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.