声敏治疗性脂质体用于临床前体内 MRI 引导下可视化多柔比星脉冲低强度非聚焦超声刺激释放。
Sonosensitive theranostic liposomes for preclinical in vivo MRI-guided visualization of doxorubicin release stimulated by pulsed low intensity non-focused ultrasound.
机构信息
Center for Molecular Imaging, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Center for Molecular Imaging, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy; Center for Preclinical Imaging, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Ribes 5, 10010 Colleretto Giacosa (TO), Italy.
出版信息
J Control Release. 2015 Mar 28;202:21-30. doi: 10.1016/j.jconrel.2015.01.028. Epub 2015 Jan 24.
The main goal of this study was to assess the theranostic performance of a nanomedicine able to generate MRI contrast as a response to the release from liposomes of the antitumor drug Doxorubicin triggered by the local exposure to pulsed low intensity non focused ultrasounds (pLINFU). In vitro experiments showed that Gadoteridol was an excellent imaging agent for probing the release of Doxorubicin following pLINFU stimulation. On this basis, the theranostic system was investigated in vivo on a syngeneic murine model of TS/A breast cancer. MRI offered an excellent guidance for monitoring the pLINFU-stimulated release of the drug. Moreover, it provided: i) an in vivo proof of the effective release of the liposomal content, and ii) a confirmation of the therapeutic benefits of the overall protocol. Ex vivo fluorescence microscopy indicated that the good therapeutic outcome was originated from a better diffusion of the drug in the tumor following the pLINFU stimulus. Very interestingly, the broad diffusion of the drug in the tumor stroma appeared to be mediated by the presence of the liposomes themselves. The results of this study highlighted either the great potential of US-based stimuli to safely trigger the release of a drug from its nanocarrier or the associated significant therapeutic improvement. Finally, MRI demonstrated to be a valuable technique to support chemotherapy and monitoring the outcome. Furthermore, in this specific case, the theranostic agent developed has a high clinical translatability because the MRI agent utilized is already approved for human use.
本研究的主要目的是评估一种能够在脂质体释放抗癌药物阿霉素作为对局部施加脉冲低强度非聚焦超声(pLINFU)的响应时产生 MRI 对比的纳米医学的治疗诊断性能。体外实验表明,钆特醇是探测 pLINFU 刺激后阿霉素释放的出色成像剂。在此基础上,在 TS/A 乳腺癌的同种异体小鼠模型上进行了治疗诊断系统的体内研究。MRI 为监测药物的 pLINFU 刺激释放提供了出色的指导。此外,它提供了:i)体内有效释放脂质体内容物的证明,以及 ii)整个方案治疗益处的确认。离体荧光显微镜表明,良好的治疗效果源自 pLINFU 刺激后药物在肿瘤中的更好扩散。非常有趣的是,药物在肿瘤基质中的广泛扩散似乎是由脂质体本身的存在介导的。这项研究的结果突出了基于超声的刺激物安全触发药物从其纳米载体中释放的巨大潜力,或与之相关的显著治疗改善。最后,MRI 被证明是支持化疗和监测结果的有价值的技术。此外,在这种特殊情况下,开发的治疗诊断剂具有很高的临床转化潜力,因为所使用的 MRI 试剂已经获得了人类使用的批准。