Nguyen Juliane, Cooke Johann R N, Ellis Jason A, Deci Michael, Emala Charles W, Bruce Jeffrey N, Bigio Irving J, Straubinger Robert M, Joshi Shailendra
Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
J Neurooncol. 2016 May;128(1):21-28. doi: 10.1007/s11060-016-2088-y. Epub 2016 Feb 22.
The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.
内皮细胞表面和胶质瘤细胞表面阴离子脂质的相对丰度表明，利用阳离子纳米颗粒进行选择性药物递送是一种可行的策略。此外，胶质瘤的细胞外pH相对呈酸性，这表明如果纳米颗粒能够设计成在这种环境中阳离子化，肿瘤选择性可能会进一步提高。基于这些有启发性的假设，本研究的目的是确定是否可以设计纳米颗粒（20纳米）胶束，以改善其在动物模型中胶质瘤内的沉积。为了验证这一点，我们对用可光学定量染料标记的胶束进行了动脉内注射。我们观察到，与正常大脑同侧半球中的不可阳离子化胶束相比，可阳离子化胶束的沉积（终末组织浓度）显著更高。更重要的是，通过半定量荧光分析判断，我们注意到与不可阳离子化胶束相比，可阳离子化胶束在胶质瘤组织中的沉积有所增强。胶束通常能够渗透到所测试胶质瘤的核心。因此，我们得出结论，可阳离子化胶束可以构建为载体，以便在动脉内注射后促进化合物向胶质瘤的选择性递送。
