論文 - 詳細
| RRC ID | 82024 |
|---|---|
| 著者 | Shen Y, Zhong B, Zheng W, Wang D, Chen L, Song H, Pan X, Mo S, Jin B, Cui H, Zhan H, Luo F, Liu J. |
| タイトル | Rg3-lipo biomimetic delivery of paclitaxel enhances targeting of tumors and myeloid-derived suppressor cells. |
| ジャーナル | J Clin Invest |
| Abstract |
Liposomal drug delivery systems have revolutionized traditional cytotoxic drugs. However, the relative instability and toxicity of the existing liposomal drug delivery systems compromised their efficacy. Herein, we present Rg3-lipo, an innovative drug delivery system using a glycosyl moiety-enriched ginsenoside (Rg3). This system is distinguished by its glycosyl moieties exposed on the liposomal surface. These moieties imitate human cell membranes to stabilize and evade phagocytic clearance. The Rg3-lipo system loaded with paclitaxel (PTX-Rg3-lipo) demonstrated favorable bioavailability and safety in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys. With its glycosyl moieties recognizing tumor cells via the glucose transporter Glut1, PTX-Rg3-lipo inhibited gastric, breast, and esophageal cancers in human cancer cell lines, tumor-bearing mice, and patient-derived xenograft models. These glycosyl moieties selectively targeted myeloid-derived suppressor cells (MDSCs) through the glucose transporter Glut3 to attenuate their immunosuppressive effect. The mechanism study revealed that Rg3-lipo suppressed glycolysis and downregulated the transcription factors c-Maf and Mafb overcoming the MDSC-mediated immunosuppressive microenvironment and enhancing PTX-Rg3-lipo's antitumor effect. Taken together, we supply substantial evidence for its advantageous bioavailability and safety in multiple animal models, including nonhuman primates, and Rg3-lipo's dual targeting of cancer cells and MDSCs. Further investigation regarding Rg3-lipo's druggability will be conducted in clinical trials. |
| 巻・号 | 134(22) |
| 公開日 | 2024-11-15 |
| DOI | 10.1172/JCI178617 |
| PII | 178617 |
| PMID | 39545407 |
| PMC | PMC11563678 |
| MeSH | Animals Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / pharmacology Cell Line, Tumor Dogs Drug Delivery Systems Female Ginsenosides* / chemistry Ginsenosides* / pharmacokinetics Ginsenosides* / pharmacology Humans Liposomes / chemistry Macaca fascicularis* Male Mice Myeloid-Derived Suppressor Cells* / drug effects Myeloid-Derived Suppressor Cells* / metabolism Neoplasms / drug therapy Neoplasms / metabolism Neoplasms / pathology Paclitaxel* / chemistry Paclitaxel* / pharmacology Rats Rats, Sprague-Dawley Xenograft Model Antitumor Assays |
| IF | 11.864 |
| 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 | News |
| 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 | MKN45(RCB1001) MKN74(RCB1002) SH-10-TC(RCB1940) |