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ACS Biomaterials Science & Engineering · 2020 · IF 4.152

On-Chip Sonoporation-Based Flow Cytometric Magnetic Labeling

Qianwei Zhu,Weiping Ding,Shibo Li,Fenfen Li,Yi Hu,Shengnan Ya,Tianzhi Luo,Dayong Gao,Bensheng Qiu

Tracing magnetically labeled cells with magnetic resonance imaging (MRI) is an emerging and promising approach to uncover in vivo behaviors of cells in cell therapy. Today, existing methods for the magnetic labeling of cells are cumbersome and time-consuming, which has greatly limited the progress of such studies on cell therapy. Thus, in this study, using the flow cytometric loading technology, we develop a sonoporation-based microfluidic chip (i.e., a microfluidic chip integrated with ultrasound; MCU), to achieve the safe, instant, convenient, and continuous magnetic labeling of cells. For the MCU we designed, a suitable group of operating conditions for safely and efficiently loading superparamagnetic iron oxide (SPIO) nanoparticles into DC2.4 cells was identified experimentally. Under the identified operating conditions, the DC2.4 cells could be labeled in approximately 2 min with high viability (94%) and a high labeling quantity of SPIO nanoparticles (19 pg of iron per cell). In addition, the proliferative functions of the cells were also well maintained after labeling. Furthermore, the in vivo imaging ability of the DC2.4 cells labeled using the MCU was verified by injecting the labeled cells into the leg muscle of the C57BL/6 mice. The results show that the excellent imaging outcome can be continuously achieved for 7 days at a density of 106 cells/mL. This work can provide insight for the design of magnetic cell labeling devices and promote the MRI-based study of cell therapies.

CAS / MDL: 67-68-5
研究领域: 生物医学工程 · 细胞治疗 · 磁共振成像 · 纳米技术
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MOLECULAR PHARMACEUTICS · 2020 · IF 4.321

Multipotent miRNA Sponge-Loaded Magnetic Nanodroplets with Ultrasound/Magnet-Assisted Delivery for Hepatocellular Carcinoma Therapy

Wei Dong,Pengying Wu,Mengfan Qin,Shifang Guo,Huasheng Liu,Xinxing Yang,Wen He,Ayache Bouakaz,Mingxi Wan,Yujin Zong

Gene therapy is likely to be the most promising way to tackle cancer, while defects in molecular strategies and delivery systems have led to an impasse in clinical application. Here, it is found that onco-miRNAs of the miR-515 and -449 families were upregulated in hepatocellular carcinoma (HCC), and the sponge targeting miR-515 family had a significant probability to suppress cancer cell proliferation. Then, we constructed non-toxic sponge-loaded magnetic nanodroplets containing 20% C6F14 (SLMNDs-20%) that are incorporated with fluorinated superparamagnetic iron oxide nanoparticles enhancing external magnetism-assisted targeting and enabling a direct visualization of SLMNDs-20% distribution in vivo via magnetic resonance imaging monitoring. SLMNDs-20% could be vaporized by programmable focused ultrasound (FUS) activation, achieving ∼45% in vitro sponge delivery efficiency and significantly enhancing in vivo sponge delivery without a clear apoptosis. Moreover, the sponge-1-carrying SLMNDs-20% could effectively suppress proliferation of xenograft HCC after FUS exposure because sponge-1-suppressing onco-miR-515 enhanced the expression of anti-oncogenes (P21, CD22, TIMP1, NFKB, and E-cadherin) in cancer cells. The current results indicated that ultrasonic cavitation-inducing sonoporation enhanced the intracellular delivery of sponge-1 using SLMNDs-20% after magnetic-assisted accumulation, which was a therapeutic approach to inhibit HCC progression.

研究领域: 癌症生物学 · 纳米技术 · 治疗学 · 医学成像 · 分子生物学
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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Photothermal-Enhanced Phase-Transition Nanodroplets for Ultrasound-Mediated Diagnosis and Gene Transfection

Jinbiao Gao,Baiqing Yu,Chao Li,Wei Wang,Ming Xu,Zhong Cao,Xiaoyan Xie,Jie Liu

Gene therapy is one of the promising solutions in cancer therapeutics. Ultrasound-mediated gene delivery showed great potential as a noninvasive strategy for gene therapy. However, the efficiency of gene transfection and incorporation of multiple functions remain key challenges in the development of gene delivery systems. In this study, we developed perfluoropentane (PFP) and gold nanorods (AuNRs) loading nanodroplets for photothermal-enhanced ultrasound-mediated imaging and gene transfection. The nanodroplet theranostic system was formulated with fluorinated cationic poly(aspartamide) based polymer that encapsulated PFP, AuNRs, and plasmid DNA and was stabilized with a negatively charged poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) coating. The nanodroplets presented good stability, biocompatibility, and DNA binding stability. Upon treatment with both near-infrared and ultrasound energy, the photothermal and ultrasound-responsive system exerted a synergistic effect, in which strong adsorption of light induced hyperthermia that promoted the phase transition of PFP and the following ultrasound irradiation, generating strong acoustic cavitation and sonoporation, thus leading to enhanced ultrasound contrast imaging and gene transfection efficiency both in vitro and in vivo.

CAS / MDL: 111-40-0 872-50-4
研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 分子生物学 · 医学成像
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