Yasunaga Masahiro, Furuta Masaru, Ogata Koretsugu, Koga Yoshikatsu, Yamamoto Yoshiyuki, Takigahira Misato, Matsumura Yasuhiro
Division of Therapeutics Development, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Sci Rep. 2013 Oct 25;3:3050. doi: 10.1038/srep03050.
The visualisation and quantitative analysis of the native drug distribution in a pre-clinical or clinical setting are desirable for evaluating drug effects and optimising drug design. Here, using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS) with enhanced resolution and sensitivity, we compared the distribution of a paclitaxel (PTX)-incorporating micelle (NK105) with that of PTX alone after injection into tumour-bearing mice. We demonstrated optically and quantitatively that NK105 delivered more PTX to the tumour, including the centre of the tumour, while delivering less PTX to normal neural tissue, compared with injection with PTX alone. NK105 treatment yielded a greater antitumour effect and less neural toxicity in mice than did PTX treatment. The use of high-resolution MALDI-IMS may be an innovative approach for pharmacological evaluation and drug design support.
在临床前或临床环境中对天然药物分布进行可视化和定量分析，对于评估药物效果和优化药物设计是很有必要的。在此，我们使用具有更高分辨率和灵敏度的基质辅助激光解吸电离成像质谱（MALDI-IMS），比较了注射含紫杉醇（PTX）的胶束（NK105）和单独注射PTX后在荷瘤小鼠体内的分布情况。我们通过光学和定量分析证明，与单独注射PTX相比，NK105向肿瘤（包括肿瘤中心）递送了更多的PTX，而向正常神经组织递送的PTX较少。与PTX治疗相比，NK105治疗在小鼠中产生了更大的抗肿瘤效果和更小的神经毒性。使用高分辨率MALDI-IMS可能是一种用于药理学评估和药物设计支持的创新方法。
