| Title |
Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo
|
|---|---|
| Published in |
International Journal of Nanomedicine, March 2017
|
| DOI | 10.2147/ijn.s120847 |
| Pubmed ID | |
| Authors |
You-Sin Jian, Ching-Wen Chen, Chih-An Lin, Hsiu-Ping Yu, Hua-Yang Lin, Ming-Yuan Liao, Shu-Huan Wu, Yan-Fu Lin, Ping-Shan Lai |
| Abstract |
Carrier-mediated drug delivery systems are promising therapeutics for targeted delivery and improved efficacy and safety of potent cytotoxic drugs. Nimesulide is a multifactorial cyclooxygenase 2 nonsteroidal anti-inflammatory drug with analgesic, antipyretic and potent anticancer properties; however, the low solubility of nimesulide limits its applications. Drugs conjugated with hyaluronic acid (HA) are innovative carrier-mediated drug delivery systems characterized by CD44-mediated endocytosis of HA and intracellular drug release. In this study, hydrophobic nimesulide was conjugated to HA of two different molecular weights (360 kDa as HA with high molecular weight [HAH] and 43kDa as HA with low molecular weight [HAL]) to improve its tumor-targeting ability and hydrophilicity. Our results showed that hydrogenated nimesulide (N-[4-amino-2-phenoxyphenyl]methanesulfonamide) was successfully conjugated with both HA types by carbodiimide coupling and the degree of substitution of nimesulide was 1%, which was characterized by (1)H nuclear magnetic resonance 400 MHz and total correlation spectroscopy. Both Alexa Fluor(®) 647 labeled HAH and HAL could selectively accumulate in CD44-overexpressing HT-29 colorectal tumor area in vivo, as observed by in vivo imaging system. In the in vitro cytotoxic test, HA-nimesulide conjugate displayed >46% cell killing ability at a nimesulide concentration of 400 µM in HT-29 cells, whereas exiguous cytotoxic effects were observed on HCT-15 cells, indicating that HA-nimesulide causes cell death in CD44-overexpressing HT-29 cells. Regarding in vivo antitumor study, both HAL-nimesulide and HAH-nimesulide caused rapid tumor shrinkage within 3 days and successfully inhibited tumor growth, which reached 82.3% and 76.4% at day 24 through apoptotic mechanism in HT-29 xenografted mice, without noticeable morphologic differences in the liver or kidney, respectively. These results indicated that HA-nimesulide with improved selectivity through HA/CD44 receptor interactions has the potential to enhance the therapeutic efficacy and safety of nimesulide for cancer treatment. |
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 % |
|---|---|---|
| Unknown | 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 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 64 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 14% |
| Student > Master | 9 | 14% |
| Student > Ph. D. Student | 8 | 13% |
| Student > Bachelor | 4 | 6% |
| Professor | 4 | 6% |
| Other | 7 | 11% |
| Unknown | 23 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 11% |
| Chemistry | 7 | 11% |
| Biochemistry, Genetics and Molecular Biology | 4 | 6% |
| Agricultural and Biological Sciences | 4 | 6% |
| Other | 6 | 9% |
| Unknown | 27 | 42% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. 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 21 February 2024.
All research outputs
#3,345,121
of 25,385,509 outputs
Outputs from International Journal of Nanomedicine
#187
of 4,123 outputs
Outputs of similar age
#59,196
of 324,479 outputs
Outputs of similar age from International Journal of Nanomedicine
#10
of 95 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,123 research outputs from this source. They receive a mean Attention Score of 4.7. This one has done particularly well, scoring higher than 95% of its peers.
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We're also able to compare this research output to 95 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 89% of its contemporaries.