| Title |
Aptamer–drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity
|
|---|---|
| Published in |
International Journal of Nanomedicine, February 2018
|
| DOI | 10.2147/ijn.s149887 |
| Pubmed ID | |
| Authors |
Xiao-qian Dou, Hua Wang, Jing Zhang, Fang Wang, Gui-li Xu, Cheng-cheng Xu, Huan-hua Xu, Shen-si Xiang, Jie Fu, Hai-feng Song |
| Abstract |
The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs. Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay. Specificity was tested in MCF-7HER3-high, BT474HER3-high, and 293THER3-negativecells using flow cytometry and confocal microscopy. We further developed a HER3 aptamer-functionalized liposome encapsulating DOX and the efficiency of this ApDC was detected by cellular uptake analysis and cell viability assay. In MCF-7 tumor-bearing mice, tumor targeting evaluation, efficacy, toxicity and preliminary pharmocokinetic study was performed. The candidate #13 aptamer had highest affinity (Kd =98±9.7 nM) and specificity. ApDC effectively reduces the half maximal inhibitory concentration of DOX compared with lipsome-DOX and free DOX. In vivo imaging and preliminary distribution studies showed that actively targeted nanoparticles, such as Apt-Lip-DOX molecules, could facilitate the delivery of DOX into tumors in MCF-7-bearing mice. This targeted chemotherapy caused greater tumor suppression than other groups and alleviated side effects such as weight loss, low survival rate, and organ (heart and liver) injury demonstrated by H&E staining. The results indicate that targeted chemotherapy using the aptamer-drug conjugate format could provide better tolerability and efficacy compared with non-targeted delivery in relatively low-dose toxic drugs. |
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 81 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 81 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 16 | 20% |
| Researcher | 14 | 17% |
| Student > Master | 13 | 16% |
| Student > Ph. D. Student | 9 | 11% |
| Other | 5 | 6% |
| Other | 6 | 7% |
| Unknown | 18 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 15 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 11% |
| Chemistry | 8 | 10% |
| Engineering | 6 | 7% |
| Agricultural and Biological Sciences | 4 | 5% |
| Other | 10 | 12% |
| Unknown | 29 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 07 March 2018.
All research outputs
#19,951,180
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#2,971
of 4,122 outputs
Outputs of similar age
#324,918
of 448,849 outputs
Outputs of similar age from International Journal of Nanomedicine
#50
of 83 outputs
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