| Title |
Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance
|
|---|---|
| Published in |
International Journal of Nanomedicine, July 2018
|
| DOI | 10.2147/ijn.s150017 |
| Pubmed ID | |
| Authors |
Fateme Haghiralsadat, Ghasem Amoabediny, Samira Naderinezhad, Behrouz Zandieh-Doulabi, Tymour Forouzanfar, Marco N Helder |
| Abstract |
Osteosarcoma (OS) mostly affects children and young adults, and has only a 20%-30% 5-year survival rate when metastasized. We aimed to create dual-targeted (extracellular against EphA2 and intracellular against JNK-interacting protein 1 [JIP1]), doxorubicin (DOX)-loaded liposomes to treat OS metastatic disease. Cationic liposomes contained N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and distearoyl-phosphatidylethanolamine-methyl-poly(ethylene glycol) (DSPE-mPEG) conjugate. EphA2 targeting was accomplished by conjugating YSA peptide to DSPE-mPEG. Vesicles were subsequently loaded with DOX and JIP1 siRNA. Characteristics assessment showed that 1) size of the bilayered particles was 109 nm; 2) DOX loading efficiency was 87%; 3) siRNA could be successfully loaded at a liposome:siRNA ratio of >24:1; and 4) the zeta potential was 18.47 mV. Tumor-mimicking pH conditions exhibited 80% siRNA and 50.7% DOX sustained release from the particles. Stability studies ensured the protection of siRNA against degradation in serum. OS cell lines showed increased and more pericellular/nuclear localizations when using targeted vesicles. Nontargeted and targeted codelivery caused 70.5% and 78.6% cytotoxicity in OS cells, respectively (free DOX: 50%). Targeted codelivery resulted in 42% reduction in the siRNA target, JIP1 mRNA, and 46% decrease in JIP1 levels. Our dual-targeted, DOX-loaded liposomes enhance toxicity toward OS cells and may be effective for the treatment of metastatic OS. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 51 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 14% |
| Student > Master | 6 | 12% |
| Professor > Associate Professor | 4 | 8% |
| Student > Bachelor | 3 | 6% |
| Student > Postgraduate | 3 | 6% |
| Other | 9 | 18% |
| Unknown | 19 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 8 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 10% |
| Agricultural and Biological Sciences | 3 | 6% |
| Nursing and Health Professions | 2 | 4% |
| Medicine and Dentistry | 2 | 4% |
| Other | 5 | 10% |
| Unknown | 26 | 51% |
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 30 July 2018.
All research outputs
#16,728,456
of 25,385,509 outputs
Outputs from International Journal of Nanomedicine
#2,087
of 4,122 outputs
Outputs of similar age
#210,510
of 341,606 outputs
Outputs of similar age from International Journal of Nanomedicine
#30
of 63 outputs
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