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    Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma
    (Basel : MDPI, 2023) Förster, Sarah; Niu, Yuequn; Eggers, Benedikt; Nokhbehsaim, Marjan; Kramer, Franz-Josef; Bekeschus, Sander; Mustea, Alexander; Stope, Matthias B.
    Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management.
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    Emerging Roles of 1D Vertical Nanostructures in Orchestrating Immune Cell Functions
    (Hoboken, NJ : Wiley, 2020) Chen, Yaping; Wang, Ji; Li, Xiangling; Hu, Ning; Voelcker, Nicolas H.; Xie, Xi; Elnathan, Roey
    Engineered nano–bio cellular interfaces driven by 1D vertical nanostructures (1D‐VNS) are set to prompt radical progress in modulating cellular processes at the nanoscale. Here, tuneable cell–VNS interfacial interactions are probed and assessed, highlighting the use of 1D‐VNS in immunomodulation, and intracellular delivery into immune cells—both crucial in fundamental and translational biomedical research. With programmable topography and adaptable surface functionalization, 1D‐VNS provide unique biophysical and biochemical cues to orchestrate innate and adaptive immunity, both ex vivo and in vivo. The intimate nanoscale cell–VNS interface leads to membrane penetration and cellular deformation, facilitating efficient intracellular delivery of diverse bioactive cargoes into hard‐to‐transfect immune cells. The unsettled interfacial mechanisms reported to be involved in VNS‐mediated intracellular delivery are discussed. By identifying up‐to‐date progress and fundamental challenges of current 1D‐VNS technology in immune‐cell manipulation, it is hoped that this report gives timely insights for further advances in developing 1D‐VNS as a safe, universal, and highly scalable platform for cell engineering and enrichment in advanced cancer immunotherapy such as chimeric antigen receptor‐T therapy.
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    Cellular Deformations Induced by Conical Silicon Nanowire Arrays Facilitate Gene Delivery
    (Weinheim : Wiley-VCH, 2019) Chen, Y.; Aslanoglou, S.; Gervinskas, G.; Abdelmaksoud, H.; Voelcker, N.H.; Elnathan, R.
    Engineered cell–nanostructured interfaces generated by vertically aligned silicon nanowire (SiNW) arrays have become a promising platform for orchestrating cell behavior, function, and fate. However, the underlying mechanism in SiNW-mediated intracellular access and delivery is still poorly understood. This study demonstrates the development of a gene delivery platform based on conical SiNW arrays for mechanical cell transfection, assisted by centrifugal force, for both adherent and nonadherent cells in vitro. Cells form focal adhesions on SiNWs within 6 h, and maintain high viability and motility. Such a functional and dynamic cell–SiNW interface features conformational changes in the plasma membrane and in some cases the nucleus, promoting both direct penetration and endocytosis; this synergistically facilitates SiNW-mediated delivery of nucleic acids into immortalized cell lines, and into difficult-to-transfect primary immune T cells without pre-activation. Moreover, transfected cells retrieved from SiNWs retain the capacity to proliferate—crucial to future biomedical applications. The results indicate that SiNW-mediated intracellular delivery holds great promise for developing increasingly sophisticated investigative and therapeutic tools. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim