Frenkel Victor, Etherington Amena, Greene Maiya, Quijano Jade, Xie Jianwu, Hunter Finie, Dromi Sergio, Li King C P
Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Building 10, Room 1N306a, 10 Center Drive, Bethesda, MD 20892, USA.
Acad Radiol. 2006 Apr;13(4):469-79. doi: 10.1016/j.acra.2005.08.024.
To investigate the potential of using pulsed high-intensity focused ultrasound (HIFU) exposures to enhance the delivery, and hence therapeutic effect of liposomal doxorubicin (Doxil) in a murine breast cancer tumor model.
Tumors were grown in the bilateral flanks of mice using a mammary adenocarcinoma cell line. Experiments consisted of exposing one of two tumors to pulsed-HIFU, followed by tail vein injections of Doxil. Tumor growth rates were monitored, and assays carried out for doxorubicin concentration in these tumors as well as in a second (squamous cell carcinoma) tumor model and in muscle. Laser scanning confocal microscopy was used with fluorescent probes to observe both the uptake of polystyrene nanoparticles and dilation of exposed blood vessels. Additional experiments involving histologic analysis and real-time temperature measurements were performed to determine the safety of the exposures.
Pulsed-HIFU exposures were shown to be safe, producing no apparent deleterious effects in the tumors. The exposures, however, were not found to enhance the delivery of Doxil, and consequently did not allow for lower doses for obtaining tumor regression. Imaging with a fluorescent dextran showed blood vessels to be dilated as a result of the exposures. Experiments with polystyrene nanoparticles of similar size to the liposomes showed a greater abundance to be present in the treated tumors.
Although past studies have shown the advantages of pulsed-HIFU exposures for enhancing delivery, this was not observed with the liposomes, apparently because of their inherent ability to preferentially accumulate into tumors on their own. Potential mechanisms for enhanced uptake of non-liposomal nanoparticles are discussed.
在小鼠乳腺癌肿瘤模型中，研究使用脉冲高强度聚焦超声（HIFU）照射来增强脂质体阿霉素（多美素）的递送并从而提高其治疗效果的潜力。
使用乳腺腺癌细胞系在小鼠双侧胁腹培育肿瘤。实验包括对两个肿瘤中的一个进行脉冲HIFU照射，随后通过尾静脉注射多美素。监测肿瘤生长速率，并对这些肿瘤以及第二个（鳞状细胞癌）肿瘤模型和肌肉中的阿霉素浓度进行测定。使用荧光探针的激光扫描共聚焦显微镜用于观察聚苯乙烯纳米颗粒的摄取以及暴露血管的扩张。进行了涉及组织学分析和实时温度测量的额外实验以确定照射的安全性。
已证明脉冲HIFU照射是安全的，在肿瘤中未产生明显的有害影响。然而，未发现照射能增强多美素的递送，因此也无法使用更低剂量来实现肿瘤消退。用荧光葡聚糖成像显示照射导致血管扩张。对与脂质体大小相似的聚苯乙烯纳米颗粒进行的实验表明，在接受治疗的肿瘤中存在更多纳米颗粒。
尽管过去的研究表明脉冲HIFU照射在增强递送方面具有优势，但在脂质体中未观察到这种情况，显然是因为脂质体自身具有优先在肿瘤中积累的固有能力。讨论了非脂质体纳米颗粒摄取增强的潜在机制。
