| RRC ID |
82024
|
| Author |
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.
|
| Title |
Rg3-lipo biomimetic delivery of paclitaxel enhances targeting of tumors and myeloid-derived suppressor cells.
|
| Journal |
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.
|
| Volume |
134(22)
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001)
MKN74(RCB1002)
SH-10-TC(RCB1940) |
