Novel biomimetic dual-mode nanodroplets as ultrasound contrast agents with potential ability of precise detection and ph

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ORIGINAL ARTICLE

Novel biomimetic dual‑mode nanodroplets as ultrasound contrast agents with potential ability of precise detection and photothermal ablation of tumors Yuan Liang1 · Hengli Yang2   · Qiaoying Li1 · Ping Zhao1 · Han Li1 · Yuxin Zhang1 · Wenbin Cai3 · Xiaoju Ma1 · Yunyou Duan1 Received: 22 April 2020 / Accepted: 4 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Purpose  Molecule-targeted ultrasound imaging has attracted extensive attention for precise diagnosis and targeted therapy of tumors. The aim of this research is to prepare novel biomimetic dual-mode nanoscale ultrasound contrast agents (UCAs), which can not only evade the immune clearance of reticuloendothelial system, but also have the potential ability of precise detection and photothermal ablation of tumors. Methods  In this study, for the first time, the novel biomimetic UCAs were prepared by encapsulating liquid perfluorohexanes with red blood cell membranes carrying IR-780 iodide and named IR780-RBCM@NDs. The characteristics of that were verified through the particle size analyzer, scanning electron microscopy, transmission electron microscopy and laser scanning confocal microscopy. The stability of IR780-RBCM@NDs at 37 °C was explored. The abilities of immune escape, dual-mode imaging and photothermal effect for IR780-RBCM@NDs were verified via in vitro experiments. Results  The novel prepared nanodroplets have good characteristics such as mean diameter, zeta potential, and relatively stability. Importantly, the integrin-associated protein expressed on the surface of RBCMs was detected on IR780-RBCM@ NDs. Then, compared with control groups, IR780-RBCM@NDs performed excellent immune escape function away from macrophages in vitro. Furthermore, the IR-780 iodide was observed on the new nanodroplets and that was able to perform the dual-mode imaging with near-infrared fluorescence imaging and contrast-enhanced ultrasound imaging after the phase change. Finally, the effective photothermal ablation ability of IR780-RBCM@NDs was verified in tumor cells. Conclusion  The newly prepared biomimetic IR780-RBCM@NDs provided novel ideas for evading immune clearance, performing precise diagnosis and photothermal ablation of tumor cells. Keywords  Red blood cell membranes · Nanodroplets · Ultrasound contrast agents · IR-780 iodide · Tumor cells

Introduction Yuan Liang, Hengli Yang and Qiaoying Li contributed equally to this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0028​0-020-04124​-x) contains supplementary material, which is available to authorized users.

The precise diagnosis and effective targeted therapy of malignant tumors could improve the survival rate of patients and help them obtain a favorable prognosis [1]. With mutual infiltration from multiple disciplines, research on malignant tumors has made rapid progress [2]. In recent

* Hengli Yang [email protected]

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Department of Ultrasound Diagnosis, The Second Affiliated Hospital, Xi’an Med