Qunqun Bao,Ping Hu,Weiwei Ren,Yuedong Guo,Jianlin Shi
Summary Surgery and subsequent chemotherapy are still the most adopted clinical modalities for bladder cancer treatments with the inevitable operation risks, chemotherapy toxicity, and high recurrence rate. Here, we report an unprecedented tumor cell dissociation strategy for malignant bladder tumor removal without the needs of conventional surgery and chemotherapy. A common metal ion chelator, ethylene diamine tetraacetic acid (EDTA), has been loaded into the interlayers of neurotensin (NT)-modified Zn-Al layered double hydroxide (LDH). Under the targeting by NT, such a nano-platform shows high affinity to bladder tumor cells, leading to the highly selective and efficient accumulation at the bladder tumor site. The released EDTA molecules deprive Ca 2+ from the intercellular calcium-dependent connexin by EDTA-Ca 2+ chelation, resulting in the tumor disaggregation that is then safely excreted out of body rather than killed using toxic chemodrugs, thus, ensuring excellent biosafety and extraordinarily high effectiveness.
Dielectrophoresis (DEP) as a label-free cell separation approach in microdevices has been extensively investigated for a variety of applications. 3D microelectrodes made of conducting-PDMS inherit the merit of volumetric electrodes for generating influential DEP force throughout the entire channel depth and meanwhile, exploit low-cost fabrication process by soft lithography. However, the configuration of conducting-PDMS electrodes is limited to being embedded in sidewall of flow chamber, which leads to rather low flow rate and difficulties in extension of the flow rate. We previously reported a more effective configuration with 3D interdigitated electrodes made of silicon that assist cell sliding along solid tracks, yet such device requires expensive silicon dry etching and, moreover, the track appears to be patterned with non-straight and wavy outline, which not only hinders the flow rate but also allows cell sliding to occur only along its downstream side. Here we demonstrate low-cost silver-PDMS electrode-track featuring ideally straight outline that induces rather uniform drag to drive smooth cell sliding. Such design achieves live and dead cell separation at flow rate twice as that of silicon tracks with cell loading concentration 10 times higher. It also fully utilizes the track to enable cell sliding on both of the up- and down-stream sides. Notably, we also demonstrate that this track is expandable to be V-shape for more advanced bidirectional cell sliding, which is showcased here by tumor cells separation from lymphocytes at 1.2 mL/h. Such results greatly enhance the throughput as compared to the state-of-art conducting-PDMS based cell separator.
Precise and specific circulating tumor cell (CTC) isolation is heavily interfered with by blood cells and proteins. Although satisfactory results have been achieved by some cell membrane-derived platforms, the following limitations have seriously limited the commercialization potential: complex membrane composition, difficult batch difference control, inconvenient source cell expansion, etc. To overcome these limitations, artificial cell membrane camouflage made from commercialized lipids and proteins was proposed in this work. Specifically, a biotinylated phospholipid which can serve as a lipid component and provide active sites (biotin) for antibody modification, and human serum albumin (HSA), which can effectively reduce certain blood protein adsorption, were applied simultaneously to endow our immunomagnetic platform with a new biological identity. Besides, making full use of the robust lipid and protein absorption ability of graphene nanosheets (GNs), the biomimetic cell membrane can be easily integrated into the magnetic core through simple lipid and protein solution incubation. Surprisingly, the resulting artificial cell membrane camouflaged immunomagnetic nanoparticles (AIMNPs) achieved high specificity (average capture efficiency 87.0%), good sensitivity (7 model CTCs per 0.5 mL) and an enhanced anti-nonspecific absorption ability (15–105 white blood cells per 1.5 mL) in both mimic and clinical blood samples.
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