Cha Jae Min, You Dong Gil, Choi Eun Jung, Park Sang Jun, Um Wooram, Jeon Jueun, Kim Kwangmeyung, Kwon Ick Chan, Park Jae Chan, Kim Hyun Ryoung, Park Jae Hyung
J Biomed Nanotechnol. 2016 Sep;12(9):1724-33. doi: 10.1166/jbn.2016.2272.
High intensity focused ultrasound (HIFU), allowing for precise heating of the deep and local area, is emerging as the source of mild hyperthermia for delivery of doxorubicin (DOX) using thermosensitive liposomes (TSLs). Conventionally, HIFU has been used for intravascular drug release at tumor tissue by inducing mild hyperthermia immediately upon systemic administration of DOX-TSLs. This immediate heating approach (IHA), however, limits the deep penetration of DOX for high anticancer efficacy. In an attempt to maximize the accumulation of DOX at tumor, the delayed heating approach (DHA) has been explored. In this approach, DOX-TSLs were intravenously administered into the tumor-bearing mice after pre-treatment of tumor tissue with HIFU to increase vascular permeability. We developed the fatty acid-cojugated elastinlike polypeptide bearing TSL (FTSL). The DOX-loaded FTSLs had a hydrodynamic size of 142 nm. In vivo biodistribution study demonstrated that DOX-FTSLs were selectively accumulated at tumor tissue with the maximum amount of DOX at 6 h post-injection. Thereafter, the tumor tissue was heated to 42 °C to induce rapid release of DOX from FTSLs. The results have demonstrated that, compared to IHA, DHA significantly enhances the antitumor efficacy of DOX-FTSLs because of their effective penetration to tumor tissue via the enhanced permeation retention effect, followed by rapid release of DOX.
高强度聚焦超声（HIFU）能够对深部和局部区域进行精确加热，正逐渐成为一种利用热敏脂质体（TSL）递送阿霉素（DOX）的温和热疗热源。传统上，HIFU通过在全身给药DOX-TSL后立即诱导温和热疗，用于肿瘤组织的血管内药物释放。然而，这种即时加热方法（IHA）限制了DOX的深度渗透，难以实现高抗癌疗效。为了使DOX在肿瘤处的蓄积最大化，人们探索了延迟加热方法（DHA）。在这种方法中，先用HIFU预处理肿瘤组织以增加血管通透性，然后将DOX-TSL静脉注射到荷瘤小鼠体内。我们开发了带有TSL的脂肪酸共轭弹性蛋白样多肽（FTSL）。负载DOX的FTSL的流体动力学尺寸为142nm。体内生物分布研究表明，DOX-FTSL在肿瘤组织中选择性蓄积，注射后6小时DOX含量最高。此后，将肿瘤组织加热至42℃，以诱导DOX从FTSL中快速释放。结果表明，与IHA相比，DHA显著提高了DOX-FTSL的抗肿瘤疗效，因为它们通过增强渗透滞留效应有效渗透到肿瘤组织，随后DOX快速释放。
