Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer.
Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer.
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DOI：
10.1002/mabi.201600194
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发表时间：
2017-01
影响因子：
4.6
通讯作者：
Kwon GS
中科院分区：
文献类型：
--
作者：
Tomoda K;Tam YT;Cho H;Buehler D;Kozak KR;Kwon GS
曲莫司是一种含有紫杉醇(PTX)、17-烯丙氨基-17-去甲氧基格尔达霉素(17-AAG)和雷帕霉素(RAP)的多药聚合物胶束。在本研究中，我们检测了曲莫司体内外的放射增敏作用。Triolimus对A549细胞的放射增敏作用呈剂量依赖关系，在2 nM时，即使在低剂量(2Gy2)照射下，Triolimus仍表现出明显的放射增敏作用。从增敏比(SER)来看，单用PTX、联合用药和2 NM的曲安奈德具有放射增敏作用，其作用强度如下：PTX(PTX)+GT；PTX+RAP(P/R)；Triolimus(TRIO)>；PTX+17-AAG(P/17)>；17-AAG+RAP(17/R)。在活体内，分次照射15Gy后，单独输注PTX、联合用药或中剂量曲安奈德(Int.Trio：PTX/17-AAG/RAP(15/15/7.5 mg/kg)对A549肿瘤生长有明显抑制作用。值得注意的是，在分割放疗前使用大剂量的Triolimus(高三联疗法：PTX/17-AAG/RAP，60/60/30 mg/kg)可使肿瘤控制长达24周。与PTX或单纯放射治疗相比，观察到了增强的放射增敏作用，而急性毒性没有增加。这些结果表明，三苯氧胺结合放射治疗值得进一步研究。
Triolimus is a multi-drug loaded polymeric micelle containing paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP). In this study, we examined the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells were dose dependent and at 2 nM, Triolimus showed significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio (SER), PTX alone, dual drug combinations, and Triolimus treatment at 2 nM had radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17-AAG (P/17) > 17-AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17-AAG/RAP at 15/15/7.5 mg/kg) strongly inhibited A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17-AAG/RAP at 60/60/30 mg/kg) before the fractionated radiation led to tumor control for up to 24 weeks. An enhanced radiosensitizing effect was observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited.