Goal: The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. Methods: We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (TSL-DOX) delivery in mouse tumors with three HT methods (thermistor probe (T), laser (L) and water bath (WB), at 15 min and 60 min HT duration), with corroborating in vivo studies. Results: Average computer model-predicted tumor drug concentrations (μg/g) were 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 min), and 8.7(WB, 60 min). Tumor fluorescence was increased by 2.6 × (T) and 1.6 × (L) when HT duration was extended from 15 to 60 min (p < 0.05), with no increase for WB HT. Pharmacokinetic analysis confirmed that water bath HT causes rapid depletion of encapsulated TSL-DOX in systemic circulation due to the large heated tissue volume. Conclusions: Untargeted large volume HT causes poor tumor drug uptake from TSL.

中文翻译：

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非靶向大容量热疗可减少肿瘤药物从热敏脂质体中的摄取

目标：热疗 (HT) 方法对热敏脂质体 (TSL) 对肿瘤药物吸收的影响尚不清楚。方法：我们创建了逼真的三维 (3-D) 计算机模型，通过三种 HT 方法（热敏电阻探针 (T)、激光 (L) 和水浴 (WB)、在 15 分钟和 60 分钟的 HT 持续时间），有确凿的体内学习。结果：计算机模型预测的平均肿瘤药物浓度 (μg/g) 分别为 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 分钟）和 8.7（WB，60 分钟）。当 HT 持续时间从 15 分钟延长至 60 分钟 (p < 0.05) 时，肿瘤荧光增加了 2.6 × (T) 和 1.6 × (L)，而 WB HT 没有增加。药代动力学分析证实，由于加热的组织体积较大，水浴 HT 会导致体循环中封装的 TSL-DOX 快速消耗。结论：非靶向大体积 HT 导致 TSL 的肿瘤药物吸收不良。