Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Molecular & Preclinical Imaging Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
J Control Release. 2016 May 28;230:57-63. doi: 10.1016/j.jconrel.2016.03.040. Epub 2016 Apr 2.
The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use.
这项工作旨在开发一种基于 MRI 的新型治疗策略,以提高类似多柔比星脂质体制剂的抗癌疗效。通过序贯应用低强度脉冲超声刺激纳米载体中药物的肿瘤内释放,并促进其在病变部位的扩散,从而实现了这一目标。该方案在携带同源乳腺癌模型的小鼠中进行了测试。不同特性的声波的组合使得:i)药物和共包封的 MRI 造影剂(钆特醇)从肿瘤区域的血管中的脂质体中释放,和 ii)释放的物质以及完整的脂质体从肿瘤基质中外渗。在肿瘤中测量的 MR-T1 对比增强报告了阿霉素的递送和超声触发释放。所开发的方案导致肿瘤内药物浓度显著增加,进而导致病变完全消退。该方案具有良好的临床转化潜力,因为治疗剂的所有成分(多柔比星、脂质体、钆特醇)都已获得人类使用的批准。
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