Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
J Control Release. 2013 Mar 10;166(2):130-8. doi: 10.1016/j.jconrel.2012.12.007. Epub 2012 Dec 20.
Effective drug delivery to tumors requires both transport through the vasculature and tumor interstitium. Previously, it was shown that gold nanorod (GNR) mediated plasmonic photothermal therapy (PPTT) is capable of increasing the overall accumulation of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers in prostate tumors. In the present study, it is demonstrated that PPTT is also capable of increasing the distribution of these conjugates in tumors. Gadolinium labeled HPMA copolymers were administered to mice bearing prostate tumors immediately before treatment of the right tumor with PPTT. The left tumor served as internal, untreated control. Magnetic resonance imaging (MRI) of both tumors showed that PPTT was capable of improving the tumor mass penetration of HPMA copolymers. Thermal enhancement of delivery, roughly 1.5-fold, to both the tumor center and periphery was observed. Confocal microscopy of fluorescently labeled copolymers corroborates these findings in that PPTT is capable of delivering more HPMA copolymers to the tumor's center and periphery. These results further demonstrate that PPTT is a useful tool to improve the delivery of polymer-drug conjugates.
有效的肿瘤药物输送需要通过血管和肿瘤间质进行运输。以前已经表明,金纳米棒(GNR)介导的等离子体光热疗法(PPTT)能够增加前列腺肿瘤中 N-(2-羟丙基)甲基丙烯酰胺(HPMA)共聚物的总体积累。在本研究中,还证明了 PPTT 也能够增加这些缀合物在肿瘤中的分布。将钆标记的 HPMA 共聚物施用于患有前列腺肿瘤的小鼠,然后立即在右肿瘤上进行 PPTT 治疗。左肿瘤作为内部、未经处理的对照。对两个肿瘤的磁共振成像(MRI)显示,PPTT 能够改善 HPMA 共聚物对肿瘤质量的穿透。观察到肿瘤中心和外围的递送热增强约 1.5 倍。荧光标记共聚物的共焦显微镜证实了这些发现,即 PPTT 能够将更多的 HPMA 共聚物递送到肿瘤的中心和外围。这些结果进一步表明,PPTT 是一种有用的工具,可以改善聚合物-药物缀合物的递送。