Chol-CTPP 是一种对血脑屏障 (BBB) 和胶质瘤 （glioma） 细胞具有双重靶向作用的配体，能与 Chol-TPP 合成Lip-CTPP 。 Lip-CTPP 是发挥阿霉素 (DOX) 和氯胺达明 (LND) 联合抗胶质瘤 (anti-glioma) 作用的潜在载体。Lip-CTPP 可提高对肿瘤细胞增殖、迁移和侵袭的抑制率，促进细胞凋亡 (apoptosis) 和坏死 (necrosis)，干扰线粒体功能。
| 生物活性 | Chol-CTPP is a ligand with dual targeting effect on blood-brain barrier (BBB) andgliomacells. Lip-CTPP can be gained by Chol-CTPP and another mitochondria targeting ligand (Chol-TPP). Lip-CTPP is a promising potential carrier to exert theanti-gliomaeffect of doxorubicin (DOX) and lonidamine (LND) collaboratively. Lip-CTPP elevates the inhibition rate of tumor cell proliferation, migration and invasion, promoteapoptosisandnecrosis, and interfere with mitochondrial function[1]. |
| IC50& Target | |
体外研究
(In Vitro) | Lip-CTPP shows satisfying cellular uptake and mitochondrial uptake[1].
Lip-CTPP (0-20 μg/mL DOX and LND, 24 h) shows cytotoxicity and induces apoptosis in C6 cells[1].
Lip-CTPP inhibits intracellular ATP production and has the most severe damage on the membrane potential of mitochondria[1].
Lip-CTPP possesses excellent potential to induce ROS generation[1].
Lip-CTPP (0.5 μg/mL DOX, 48 h) exhibits strong inhibitory effect both on cell migration and invasion[1]
Cell Cytotoxicity Assay[1] | Cell Line: | C6 cells | | Concentration: | 0.1, 0.5, 2.5, 5, 10, and 20 μg/mL of DOX and LND | | Incubation Time: | 24 h | | Result: | Showed cytotoxicity on C6 cells in a concentration-dependent manner. |
Apoptosis Analysis[1] | Cell Line: | C6 cells | | Concentration: | 0.5 μg/mL DOX and LND | | Incubation Time: | 24 h | | Result: | Performed excellent lethality on C6 cells and the apoptosis and necrosis rate is 3.4 times that of Free DOX + LND. |
Cell Invasion Assay[1] | Cell Line: | C6 cells | | Concentration: | 0.5 μg/mL DOX | | Incubation Time: | 48 h | | Result: | Obviously restricted the invasion of C6 cells. |
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体内研究
(In Vivo) | Lip-CTPP (3 mg/kg DOX and LND; i.v.; once on day 4, 7, 10 and 13) induces glioma cells apoptosis and inhibits tumor growth[1].
Lip-CTPP can slow down the clearance of free drugs and enhance tumor targeting properties[1].
| Animal Model: | Kunming mice (male, 20-25 g), 5 μL of C6 cells (2 × 108 cells/mL) were injected into the striatum[1] | | Dosage: | 3 mg/kg DOX and LND | | Administration: | Tail vein injection, once on day 4, 7, 10 and 13 | | Result: | Increased the survival time, decreased tumor area and the density of tumor cells. |
| Animal Model: | Kunming mice (20-25 g)[1] | | Dosage: | 10 mg/kg DOX and LND | | Administration: | Tail vein injection (Pharmacokinetics Analysis) | | Result: | Pharmacokinetic parameters of DOX in blood after administration (mean ± SD, n = 3)[1]
| parameters | AUC(0-t)
(μg/mL*min) | MRT (min) | Tmax(min) | Cmax(μg/mL) | t1/2(min) | Clz (L/min/kg) | | Lip-CTPP | 5901.90 ± 406.18 | 291.30 ± 1.18 | 30 | 23.31 ± 0.42 | 231.06 ± 43.35 | 1.68 ± 0.13 |
Pharmacokinetic parameters of DOX in brain after administration (mean ± SD, n = 3)[1]
| parameters | AUC(0-t)
(μg/mL*min) | MRT (min) | Tmax(min) | Cmax(μg/mL) | t1/2(min) | Clz (L/min/kg) | | Lip-CTPP | 1757.61 ± 19.35 |
| | 分子量 | | | Formula | | | 运输条件 | Room temperature in continental US; may vary elsewhere. | | 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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