論文 - 詳細
| RRC ID | 86068 |
|---|---|
| 著者 | Kumar S, Koseki Y, Tanita K, Shibata A, Mizutani A, Kasai H. |
| タイトル | SN-38-indoximod conjugate: carrier free nano-prodrug for cancer therapy. |
| ジャーナル | Ther Deliv |
| Abstract |
BACKGROUND:The integration of immunotherapy alongside chemotherapy represents a crucial approach in the treatment of cancer. Herein we report the SN-38-indoximod conjugate nano-prodrug to address the difficulties encountered by individuals. In this prodrug, SN-38 is connected to indoximod through a specific disulfide linker, which enables the release of the components in response to the tumor microenvironment characterized by elevated levels of glutathione, thereby facilitating programmed chemoimmunotherapy. RESULTS:SN-38-indoximod conjugate was synthesized and fabricated to nano-prodrug by reprecipitation method. It showed comparable anti-cancer activity against A549 cells than SN-38 (IC50 = 0.24 ± 0.01 µM) with IC50 value 0.32 ± 0.04 µM. It inhibited 90% A549 cell at very lower concentration (IC90 = 6.07 ± 0.41 µM) as compared with SN-38 (IC90 = 24.60 ± 1.24 µM) and mixture of SN-38: indoximod (1:1, IC90 >30 µM). The nano-prodrug showed better size distribution profile and dispersion stability contains nanoparticles in effective size range (80-160 nm) required for the EPR effect. CONCLUSION:This research offers valuable insights into the advancement of conjugate nano-prodrugs exhibiting synergistic pharmacological effects, while also presenting novel opportunities for the design of prodrug molecules capable of releasing drugs in response to diverse triggers. |
| 巻・号 | 16(3) |
| ページ | 217-226 |
| 公開日 | 2025-3-1 |
| DOI | 10.1080/20415990.2025.2458449 |
| PMID | 39887189 |
| PMC | PMC11875466 |
| MeSH | A549 Cells Antineoplastic Agents* / administration & dosage Antineoplastic Agents* / chemistry Antineoplastic Agents* / pharmacology Cell Line, Tumor Cell Survival / drug effects Drug Carriers / chemistry Drug Liberation Humans Nanoparticles* / chemistry Particle Size Prodrugs* / administration & dosage Prodrugs* / chemistry Prodrugs* / pharmacology Tumor Microenvironment / drug effects |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB3677) MCF7(RCB1904) |