Guangdong Provincial Key Lab of Liver Disease and Department of Medical Ultrasonic , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou 510630 , China.
Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center , University of California Davis , Sacramento , California 95817 , United States.
ACS Nano. 2018 Apr 24;12(4):3449-3460. doi: 10.1021/acsnano.8b00076. Epub 2018 Apr 13.
Among medical imaging modalities available in the clinic, ultrasonography is the most convenient, inexpensive, ionizing-radiation-free, and most common. Micrometer-size perfluorocarbon bubbles have been used as efficient contrast for intravascular ultrasonography, but they are too big for tumor penetration. Nanodroplets (250-1000 nm) encapsulating both perfluorocarbon and drug have been used as an ultrasound-triggered release drug delivery platform against cancer, but they are generally not useful as a tumor imaging agent. The present study aims to develop a type of pH-sensitive, polymersome-based, perfluorocarbon encapsulated ultrasonographic nanoprobe, capable of maintaining at 178 nm during circulation and increasing to 437 nm at the acidic tumor microenvironment. Its small size allowed efficient tumor uptake. At the tumor site, the nanoparticle swells, resulting in lowering of the vaporization threshold for the perfluorocarbon, efficient conversion of nanoprobes to echogenic nano/microbubbles for ultrasonic imaging, and eventual release of doxorubicin from the theranostic nanoprobe for deep tissue chemotherapy, triggered by irradiation with low-frequency ultrasound.
在临床可用的医学成像方式中，超声成像是最便捷、最便宜、无电离辐射且最常用的。微米级的全氟碳气泡已被用作血管内超声造影的有效对比剂，但它们对于肿瘤穿透来说太大了。纳米液滴（250-1000nm）封装了全氟碳和药物，已被用作超声触发释放药物输送平台来对抗癌症，但它们通常不能作为肿瘤成像剂。本研究旨在开发一种 pH 敏感的聚合物囊泡包裹的全氟碳超声纳米探针，在循环过程中能够保持在 178nm，在酸性肿瘤微环境中增加到 437nm。其小尺寸允许其高效进入肿瘤。在肿瘤部位，纳米颗粒会膨胀，导致全氟碳的汽化阈值降低，纳米探针高效转化为声振纳米/微泡，用于超声成像，并且多柔比星最终从治疗性纳米探针中释放出来，用于深层组织化疗，这是由低频超声辐射触发的。
