4 years ago

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
Min Wu, Jian-Gang Ren, Wei Zhang, Jing-Ya Zhao, Zi-Li Yu, Gang Chen, Yi-Fang Zhao, Dai-Wen Pang, Wen-Qun Zhong, Zhi-Ling Zhang
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. Circulating microparticles (CMPs) purified from the plasma of oral cancer patients are simultaneously loaded with ultrasmall Mn-magnetofunctionalized Ag2Se quantum dots (Ag2Se@Mn QDs) and antitumor siRNA with the assistance of electroporation. Based on the dual-mode traceability of Ag2Se@Mn QDs and the inherent tumor-targeting and cargo-delivering abilities of CMPs, these real natural vectors are successfully transformed into multifunctional nanoplatforms for tumor-targeted theranostics.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201703482

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