論文 - 詳細
| RRC ID | 41668 |
|---|---|
| 著者 | Wang J, Zhang PC, Lu HF, Ma N, Wang S, Mao HQ, Leong KW. |
| タイトル | New polyphosphoramidate with a spermidine side chain as a gene carrier. |
| ジャーナル | J Control Release |
| Abstract |
A new cationic polymer (PPA-SP), polyphosphoramidate bearing spermidine side chain, was prepared as a non-viral vector for gene delivery. PPA-SP was synthesized from poly(1,2-propylene H-phosphonate) by the Atherton-Todd reaction. The weight average molecular weight of PPA-SP was 3.44x10(4) with a number average degree of polymerization of 90, as determined by GPC/LS/RI method. The average net positive charge per polymer chain was 102. PPA-SP was able to condense plasmid DNA efficiently and formed complexes at an N/P ratio (free amino groups in polymer to phosphate groups in DNA) of 2 and above, as determined by agarose gel electrophoresis. This new gene carrier offered significant protection to DNA against nuclease degradation at N/P ratios above 2, and showed lower cytotoxicity than PLL and PEI in cell culture. The LD(50) of PPA-SP was 85 microg/ml in COS-7 cells, in contrast to 20 and 42 microg/ml for PLL and PEI, respectively. The complexes prepared in saline at N/P ratios of 5 approximately 10 had an average size of 250 nm and zeta-potential of 26 mV. PPA-SP mediated efficient gene transfection in a number of cell lines, and the transfection protocol was optimized in HEK293 cells using a luciferase plasmid as a marker gene. Gene expression mediated by PPA-SP was greatly enhanced when chloroquine was used in conjunction at a concentration of 100 microM. Under the optimized condition, PPA-SP/DNA complexes yield a luciferase expression level closed to PEI/DNA complexes or Transfast mediated transfection. In a non-invasive CNS gene delivery model, PPA-SP/DNA complexes yielded comparable bcl-2 expression as PEI/DNA complexes in mouse brain stem following injection of the complexes in the tongue. |
| 巻・号 | 83(1) |
| ページ | 157-68 |
| 公開日 | 2002-9-18 |
| DOI | 10.1016/s0168-3659(02)00180-3 |
| PII | S0168365902001803 |
| PMID | 12220847 |
| MeSH | Animals COS Cells / drug effects COS Cells / metabolism Chlorocebus aethiops Drug Carriers / administration & dosage* Drug Carriers / chemistry Drug Carriers / pharmacokinetics Female Genetic Therapy / methods* Humans Mice Mice, Inbred BALB C Polymers / administration & dosage* Polymers / chemistry Polymers / pharmacokinetics Spermidine / administration & dosage* Spermidine / chemistry Spermidine / pharmacokinetics Tumor Cells, Cultured / drug effects Tumor Cells, Cultured / metabolism |
| IF | 7.727 |
| 引用数 | 100 |
| WOS 分野 | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 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 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HuH-7(RCB1366) |