Development of a Dual-Modally Traceable Nanoplatform for Cancer Theranostics Using Natural Circulating Cell-Derived Microparticles in Oral Cancer Patients
Development of a Dual-Modally Traceable Nanoplatform for Cancer Theranostics Using Natural Circulating Cell-Derived Microparticles in Oral Cancer Patients
复制标题
使用天然循环细胞衍生的微粒在口腔癌患者中开发用于癌症治疗诊断的双模态可追踪纳米平台
DOI：
10.1002/adfm.201703482
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发表时间：
2017
影响因子：
19
通讯作者：
Chen Gang
中科院分区：
文献类型：
--
作者：
Yu Zi Li;Zhang Wei;Zhao Jing Ya;Zhong Wen Qun;Ren Jian Gang;Wu Min;Zhang Zhi Ling;Pang Dai Wen;Zhao Yi Fang;Chen Gang
细胞衍生微粒（MP）是在细胞之间传递生物活性分子的生物纳米膜囊泡，具有作为治疗平台的巨大潜力。然而，到目前为止，在先前的研究中用作治疗诊断载体的所有MP都是在体外从细胞培养上清液中产生的，这仍然与关于实际应用的几个问题有关。在这项研究中，从口腔鳞状细胞癌（OSCC）患者外周血中新鲜纯化的循环MP（CMP）通过电穿孔直接有效地嵌入超小近红外荧光磁性量子点（Ag2Se@Mn QD）。凭借Ag2Se@Mn QD标记的CMP的上级光稳定性、良好的生物相容性和体内双模式可追溯性，首次在活体小鼠中直接可视化来自OSCC患者的CMP的组织分布和天然肿瘤靶向行为。此外，通过将抗肿瘤siRNA和Ag2Se@Mn QD同时嵌入来自OSCC患者的CMP中，开发了用于癌症治疗诊断的双模式可追踪和主动肿瘤靶向纳米平台。这项研究报告了第一个可靠的无缀合标记策略，用于体内双模式追踪从人体收集的CMP，更重要的是，报告了基于来自癌症患者的天然存在的CMP的可追踪肿瘤靶向治疗诊断载体的开发。
Cell‐derived microparticles (MPs), which are biogenic nanosized membrane vesicles that convey bioactive molecules between cells, have exhibited great potential to serve as therapeutic platforms. However, so far, all the MPs used as theranostic vectors in previous studies have been produced in vitro from cell culture supernatants, which is still associated with several concerns regarding practical applications. In this study, circulating MPs (CMPs), which are freshly purified from the peripheral blood of oral squamous cell carcinoma (OSCC) patients, are directly and efficiently embedded with ultrasmall near‐infrared‐fluorescent magnetic quantum dots (Ag2Se@Mn QDs) via electroporation. By virtue of the superior photostability, favorable biocompatibility, and dual‐mode traceability of Ag2Se@Mn QD‐labeled CMPs in vivo, the tissue distribution and natural tumor‐targeting behavior of CMPs from OSCC patients are directly visualized in living mice for the first time. Moreover, by simultaneously embedding antitumor siRNA and Ag2Se@Mn QDs into CMPs derived from OSCC patients, a dual‐modally traceable and actively tumor‐targeted nanoplatform for cancer theranostics is developed. This study reports the first reliable conjugation‐free labeling strategy for in vivo dual‐mode tracking of CMPs harvested from the human body, and, more importantly, reports the development of traceable tumor‐targeted theranostic vectors based on naturally occurring CMPs from cancer patients.