論文 - 詳細
| RRC ID | 19234 |
|---|---|
| 著者 | Wang C, Ho PC, Lim LY. |
| タイトル | Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells. |
| ジャーナル | Int J Pharm |
| Abstract |
The purpose of this study was to investigate the potentiation of the anticancer activity and enhanced cellular retention of paclitaxel-loaded PLGA nanoparticles after surface conjugation with wheat germ agglutinin (WGA) against colon cancer cells. Glycosylation patterns of representative colon cancer cells confirmed the higher expression levels of WGA-binding glycoproteins in the Caco-2 and HT-29 cells, than in the CCD-18Co cells. Cellular uptake and in vitro cytotoxicity of WNP (final formulation) against colon cell lines was evaluated alongside control formulations. Confocal microscopy and quantitative analysis of intracellular paclitaxel were used to monitor the endocytosis and retention of nanoparticles inside the cells. WNP showed enhanced anti-proliferative activity against Caco-2 and HT-29 cells compared to corresponding nanoparticles without WGA conjugation (PNP). The greater efficacy of WNP was associated with higher cellular uptake and sustained intracellular retention of paclitaxel, which in turn was attributed to the over-expression of N-acetyl-D-glucosamine-containing glycoprotein on the colon cell membrane. WNP also demonstrated increased intracellular retention in the Caco-2 (30% of uptake) and HT-29 (40% of uptake) cells, following post-uptake incubation with fresh medium, compared to the unconjugated PNP nanoparticles (18% in Caco-2) and (27% in HT-29), respectively. Cellular trafficking study of WNP showed endocytosed WNP could successful escape from the endo-lysosome compartment and release into the cytosol with increasing incubation time. It may be concluded that WNP has the potential to be applied as a targeted delivery platform for paclitaxel in the treatment of colon cancer. |
| 巻・号 | 400(1-2) |
| ページ | 201-10 |
| 公開日 | 2010-11-15 |
| DOI | 10.1016/j.ijpharm.2010.08.023 |
| PII | S0378-5173(10)00653-8 |
| PMID | 20804835 |
| MeSH | Antineoplastic Agents, Phytogenic / administration & dosage Antineoplastic Agents, Phytogenic / pharmacokinetics Antineoplastic Agents, Phytogenic / pharmacology* Biological Transport Cell Line, Tumor Cell Proliferation / drug effects Chemistry, Pharmaceutical Colonic Neoplasms / metabolism* Drug Delivery Systems Drug Screening Assays, Antitumor Endocytosis Humans Lactic Acid / chemistry* Lactic Acid / toxicity Nanoparticles* Paclitaxel / administration & dosage Paclitaxel / pharmacokinetics Paclitaxel / pharmacology* Polyglycolic Acid / chemistry* Polyglycolic Acid / toxicity Polylactic Acid-Polyglycolic Acid Copolymer Wheat Germ Agglutinins / chemistry* Wheat Germ Agglutinins / pharmacokinetics Wheat Germ Agglutinins / toxicity |
| IF | 4.845 |
| 引用数 | 40 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |