Hyperthermia-triggered drug delivery from iRGD-modified temperature-sensitive liposomes enhances the anti-tumor efficacy using high intensity focused ultrasound
Hyperthermia-triggered drug delivery from iRGD-modified temperature-sensitive liposomes enhances the anti-tumor efficacy using high intensity focused ultrasound
复制标题
使用高强度聚焦超声从 iRGD 修饰的温度敏感脂质体中热触发药物递送增强抗肿瘤功效
DOI：
10.1016/j.jconrel.2016.10.030
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发表时间：
2016-12-10
影响因子：
10.8
通讯作者：
Zheng, Hairong
中科院分区：
文献类型：
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作者：
Deng, Zhiting;Xiao, Yang;Zheng, Hairong
化疗成功治疗癌症的一个重要限制是无法在避免健康组织损伤的同时达到治疗有效的药物浓度。本工作采用新型肿瘤靶向肽iRGD（CCRGDKGPDC）修饰载药低温敏感脂质体（iRGD-LTSL-DOX），探讨其与高强度聚焦超声（HIFU）联合的体外和体内抗肿瘤作用。 iRGD-LTSL-DOX 可以特异性靶向 alpha nu beta 3 阳性细胞，并以热疗触发方式局部释放封装的阿霉素 (DOX)。体内结果表明，在HIFU触发热处理后，iRGD-LTSL-DOX的DOX在血管内释放并快速渗透到肿瘤间隙，从而克服了抗癌药物的肿瘤渗透有限。显着更强的抗肿瘤功效进一步支持了 iRGD-LTSL-DOX 与 HIFU 诱导热疗的有效组合。我们的研究提供了一种新型肿瘤靶向 LTSL-DOX，并证明了其在 HIFU 诱导的高热触发药物输送中的有用性。 (C) 2016 Elsevier B.V. 保留所有权利。
An important limitation to successful cancer treatment with chemotherapeutics is the inability to achieve therapeutically effective drug concentrations while avoiding healthy tissue damage. In this work, a new tumor-targeting peptide iRGD (CCRGDKGPDC) was used to modify drug-loaded low temperature-sensitive liposomes (iRGD-LTSL-DOX) to explore the anti-tumor effects in combination with high intensity focused ultrasound (HIFU) in vitro and in vivo. iRGD-LTSL-DOX can specifically target to alpha nu beta 3-positive cells and locally release the encapsulated doxorubicin (DOX) in a hyperthermia-triggered manner. In vivo results showed that DOX from iRGD-LTSL-DOX was intravascularly released and rapidly penetrated into tumor interstitial space after HIFU-triggered heat treatment, thereby overcoming the limited tumor penetration of anticancer drugs. Significantly stronger anti-tumor efficacy further supported the effective combination of iRGD-LTSL-DOX with HIFU-induced hyperthermia. Our study provided a novel tumor-targeting LTSL-DOX and demonstrated its usefulness in HIFU-induced hyperthermia-triggered drug delivery. (C) 2016 Elsevier B.V. All rights reserved.