The synergistic strategy based on magnetic hyperthermia and free radical therapy demonstrates tremendous potential in inducing effective tumor cell death. Therefore, the development of a novel multifunctional micromotor with magnetic-thermal dual responsiveness is of paramount importance. Here, a novel silicon-based tubular micromotor (SiMMs) is presented, which is fabricated via template-assisted atomic layer deposition (ALD). The SiMMs is specially designed to load 2,2’-azobis(2-midinopropane) dihydrochloride (AAPH), which is an anticancer drug. Firstly, the micromotors were prepared using a polycarbonate (PC) film as a template to grow silicon microtubes via ALD. Then, a multi-step functionalization process was carried out, the silicon microtubes were modified with Fe3O4 magnetic nanoparticles and gold core–silver shell nanoparticles to enable magnetic controllability and surface-enhanced Raman scattering (SERS) traceability. Subsequently, aptamers and AAPH were further modified onto the microtubes through a coupling method. Finally, characterizations of SiMMs were conducted, including motion behaviors, fluorescence and SERS signals. Magnetic–hyperthermia synergistic therapy of cancer cells using SiMMs were also investigated. Results indicated that SiMMs exhibit excellent magnetic controllability, targeted drug delivery efficiency, real-time monitoring capabilities, and outstanding cytotoxicity towards cancer cells under an alternating magnetic field (AMF). The novel SiMMs-based drug carrier and synergistic treatment strategy provide a new platform for cancer therapy.
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Glucose detection in complex matrix such as physiological fluids and drinks can provide useful information guide for people. However, traditional detection methods toward complex matrix suffer from the impurity interference or complex pretreatments. So, it is important to exploit a universal and sensitive glucose detection strategy in complex matrix. In this work, a cascade catalytic scheme based on peroxidase-like MBs@MIL-100(Fe)@Ag (MMA) is developed for sensitive glucose detection in complex solution. Using 3,3’,5,5’-tetramethylbenzidine (TMB) as an indicator, MMA can trigger catalytic cascade reactions for specific glucose sensing. In particular, the peroxidase-like MIL-100(Fe) serves as both the catalysis unit and enrichment unit. Oxidation state of TMB (oxTMB) can be effectively and specifically enriched by MIL-100(Fe) to exclude the interference of undesired impurities and macromolecules, which is suitable for complex sample matrix including colored soda and saliva. In addition, utilizing the peroxidase-like activity of MIL-100(Fe) for self-clean, the residual indicator molecules can be degraded, resulting in the recyclable use of MMA.
Emerging single-cell technologies create new opportunities for unraveling tumor heterogeneity. However, the development of high-content phenotyping platform is still at its infancy. Here, we develop a microfluidic chip for two-dimensional (2D) profiling of tumor chemotactic and molecular features at single cell resolution. Individual cells were captured by the triangular micropillar arrays in the cell-loading channel, facilitating downstream single-cell analysis. For 2D phenotyping, the chemotactic properties of tumor cells were visualized through cellular migratory behavior in microchannels, while their protein expression was profiled with multiplex surface enhanced Raman scattering (SERS) nanovectors, in which Raman reporter-embedded gold@silver core–shell nanoparticles (Au@Ag REPs) were modified with DNA aptamers targeting cellular surface proteins. As a proof of concept, breast cancer cells with diverse phenotypes were tested on the chip, demonstrating the capability of this platform for simultaneous chemotactic and molecular analysis. The chip is expected to provide a powerful tool for investigating tumor heterogeneity and promoting clinical precision medicine.
Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell–cell communications. Here, we combined surface-enhanced Raman scattering (SERS) nanoprobes with microfluidic networks to monitor in situ the cancer–immune system intercellular communications. The microfluidic platform links up immune cells with cancer cells, where the cancer-cell secretions act as signaling mediators. First, gold@silver core–shell nanorods were employed to fabricate SERS immunoprobes for analysis of the signaling molecules. Multiple cancer secretions in a tumor microenvironment were quantitatively analyzed by a SERS-assisted three-dimensional (3D) barcode immunoassay with high sensitivity (1 ng/mL). Second, in an on-chip cell proliferation assay, multiple immunosuppressive proteins secreted by cancer cells were found to inhibit activation of immune cells, indicating that the platform simulates the physiological process of cancer–immune system communications. Furthermore, potential drug candidates were tested on this platform. A quantitative SERS immunoassay was performed to evaluate drug efficacy at regulating the secretion behavior of cancer cells and the activity of immune cells. This assay showed the suitability of this platform for in vitro drug screening. It is expected that the fully integrated and highly automated SERS-microfluidic platform will become a powerful analytical tool for probing intercellular communications and should accelerate the discovery and clinical validation of novel drugs.