論文 - 詳細
| RRC ID | 67714 |
|---|---|
| 著者 | Kudo S, Nagasaki Y. |
| タイトル | A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles. |
| ジャーナル | J Control Release |
| Abstract |
In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy. |
| 巻・号 | 217 |
| ページ | 256-62 |
| 公開日 | 2015-11-10 |
| DOI | 10.1016/j.jconrel.2015.09.019 |
| PII | S0168-3659(15)30121-8 |
| PMID | 26386436 |
| MeSH | Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacokinetics Cell Line, Tumor Macrophages / drug effects* Macrophages / metabolism Male Mice, Inbred BALB C Nanoparticles / administration & dosage* Nanoparticles / chemistry Neoplasms / drug therapy Neoplasms / metabolism Neoplasms / pathology Nitric Oxide / metabolism* Nitric Oxide Synthase Type II / metabolism Peptides / administration & dosage* Peptides / chemistry Peptides / pharmacokinetics Polyethylene Glycols / administration & dosage* Polyethylene Glycols / chemistry Polyethylene Glycols / pharmacokinetics Tumor Burden / drug effects |
| IF | 7.727 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | Colon-26(RCB2657) |