School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Colloids Surf B Biointerfaces. 2019 Feb 1;174:416-425. doi: 10.1016/j.colsurfb.2018.11.046. Epub 2018 Nov 20.
Ultrasound-triggered delivery system is among the various multifunctional and stimuli-responsive strategies that hold great potential as a robust solution to the challenges of localized drug delivery and gene therapy. In this work, we developed an ultrasound-triggered delivery system PFP/CF-PAsp(DET)/CAD/PGA-g-mPEG nanodroplet, which combined ultrasound responsive phase-change contrast agent, acid-cleavable doxorubicin prodrug and cationic amphiphilic fluorinated polymer carrier, aiming to achieve both high imaging contrast and preferable ultrasound-triggered anti-cancer therapeutic effect. The optimized nanodroplets were characterized as monodispersed particles with a diameter of about 400 nm, slightly positive surface charge and high drug-loading efficiency. The functional augmenter PGA-g-mPEG provided the nanodroplets good sustainability, low cytotoxicity and good serum compatibility, as confirmed by stability and biocompatibility tests. In ultrasound imaging study, the nanodroplets produced significant contrast with ultrasound irradiation (3.5 MHz, MI = 0.08) at 37 ℃. Cell uptake and cytotoxicity studies in HepG2 and CT-26 cells showed the enhanced drug uptake and therapeutic effect with the combination of nanodroplets and ultrasound irradiation. These results suggest that the PFP/CAD-loaded phase change nano-emulsion can be utilized as an efficient theranostic agent for both ultrasound contrast imaging and drug delivery.
超声触发递送系统是各种多功能和刺激响应策略之一，作为局部药物递送和基因治疗挑战的强大解决方案具有很大的潜力。在这项工作中，我们开发了一种超声触发递送系统 PFP/CF-PAsp(DET)/CAD/PGA-g-mPEG 纳米乳液，它结合了超声响应相变造影剂、酸可裂解阿霉素前药和阳离子两亲性氟聚合物载体，旨在实现高成像对比度和更优的超声触发抗癌治疗效果。优化的纳米乳液表现为粒径约为 400nm 的单分散颗粒，具有轻微的正表面电荷和高载药效率。功能增强剂 PGA-g-mPEG 提供了纳米乳液良好的可持续性、低细胞毒性和良好的血清相容性，这一点通过稳定性和生物相容性测试得到了证实。在超声成像研究中，纳米乳液在 37℃下用 3.5MHz、MI=0.08 的超声辐射产生了显著的对比。在 HepG2 和 CT-26 细胞中的细胞摄取和细胞毒性研究表明，纳米乳液与超声辐射联合使用可增强药物摄取和治疗效果。这些结果表明，载 PFP/CAD 的相变纳米乳液可用作超声对比成像和药物递送的高效治疗剂。
