The precise delivery of targeted cells through magnetic field-driven microrobots/carriers is a promising technique for targeted therapy and tissue regeneration. This paper presents a microrobot designed with a burr-like porous spherical structure for carrying and delivering targeted cells in vivo under a magnetic gradient field-driven mechanism. The robot was fabricated by using three-dimensional laser lithography and coated with Ni for magnetic actuation and Ti for biocompatibility. Numerical and experimental studies demonstrated that the proposed microrobot design could enhance magnetic driving capability, promote cell-carrying capacity, and benefit cell viability. Microrobots loaded with cells could be automatically controlled to reach a desired site by using a self-constructed electromagnetic coil system, as verified by in vivo transport of cell-cultured microrobots in zebrafish embryos. The carried cells could be spontaneously released from the microrobot to the surrounding tissues; in vitro experiments showed that cells from the microrobot were directly released onto the desired site or were able to pass through the blood vessel-like microchannel to arrive at the delivery area. Further in vivo cell-releasing tests were performed on nude mice, followed by histological study. This research provides a microrobotic device platform for regenerative medicine and cell-based therapy.
Precise delivery of therapeutic cells to the desired site in vivo is an emerging and promising cellular therapy in precision medicine. This paper presents the development of a magnet‐driven and image‐guided degradable microrobot that can precisely deliver engineered stem cells for orthotopic liver tumor treatment. The microrobot employs a burr‐like porous sphere structure and is made with a synthesized composite to fulfill degradability, mechanical strength, and magnetic actuation capability simultaneously. The cells can be spontaneously released from the microrobots on the basis of the optimized microrobot structure. The microrobot is actuated by a gradient magnetic field and guided by a unique photoacoustic imaging technology. In preclinical experiments on nude mice, microrobots carrying cells are injected via the portal vein and the released cells from the microrobots can inhibit the tumor growth greatly. This paper reveals for the first time of using degradable microrobots for precise delivery of therapeutic cells in vascular tissue and demonstrates its therapeutic effect in preclinical test.
BackgroundBenzo[a]pyrene (B[a]P) is a common environmental and foodborne pollutant. Although the carcinogenicity of high-dose B[a]P has been extensively reported, the effects of long-term B[a]P exposure at lower environmental doses on cancer development are less understood.ObjectivesWe investigated the impact of B[a]P on human hepatocellular carcinoma (HCC) progression at various levels of exposure and identified a potential intervention target.MethodsWe used a model based on human HCC cells exposed to various concentrations of B[a]P (i.e., 0.01, 1, or 100 nM) for 1 month to examine the effects of B[a]P on cell growth, migration, invasion, and angiogenicity. A bioluminescent murine model was established to assess tumor metastasis in vivo.ResultsChronic B[a]P exposure did not alter HCC cell growth but promoted cell migration and invasion both in vitro and in vivo. There was an negative association between B[a]P exposure and the survival of tumor-bearing mice. In addition, B[a]P-treated HCC cells recruited vascular endothelial cells and promoted tumor angiogenesis, possibly through elevating vascular endothelial growth factor secretion. Furthermore, the NF-κB pathway may be an adverse outcome pathway associated with the cumulative effects of B[a]P on HCC metastasis.ConclusionsThese findings a) indicate that B[a]P has effects on HCC progression; b) identify a possible adverse outcome pathway; and c) contribute to a better understanding of the adverse effects of chronic exposure of B[a]P to human health.CitationBa Q, Li J, Huang C, Qiu H, Li J, Chu R, Zhang W, Xie D, Wu Y, Wang H. 2015. Effects of benzo[a]pyrene exposure on human hepatocellular carcinoma cell angiogenesis, metastasis, and NF-κB signaling. Environ Health Perspect 123:246–254; http://dx.doi.org/10.1289/ehp.1408524
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