Inorganic nanoparticles (NPs) offer significant advantages to the biomedical field owing to their large surface area, controllable structures, diverse surface chemistry, and unique optical and physical properties. Researchers worldwide have shown that inorganic NPs and the released metal ions can act as therapeutic agents in targeted tissues or to cure various diseases without acute toxicity. In this progress report, the recent developments in inorganic NPs with different compositions directly used as therapeutics are discussed. First, the recent convergence of nanotechnology and biotechnology in biomedical applications as well as the unique functions, features, and advantages of inorganic NPs in biomedical applications are summarized. Thereafter, the biological effects of inorganic compositions in NPs which include balancing the intracellular redox environment, regulating the specific cellular signaling and cellular behaviors, and apoptosis are explained. In addition, the emerging therapeutic applications of inorganic NPs in various diseases are exemplified. Finally, the perspectives and challenges for overcoming the weaknesses of inorganic NPs as therapeutics are discussed. By carefully considering and investigating the biological effects of inorganic NPs and metal ions released from NPs, more promising inorganic NPs based therapeutic agents can be developed.
Conventional 3D cell culture methods require a comprehensive complement in laborintensive and time-consuming processes along with in vivo circumstantial mimicking.Here, we describe a subaqueous free-standing 3D cell culture (FS) device that can induce the omnidirectional environment and generate ultrafast human adiposederived stem cells (hADSCs) that efficiently aggregate with compaction using acoustic pressure. The cell culture conditions were optimized using the FS device and identified the underlying molecular mechanisms. Unique phenomena in cell aggregation have led to extraordinary cellular behavior that can upregulate cell compaction, mechanosensitive immune control, and therapeutic angiogenesis. Therefore, we designated the resulting cell aggregates as "pressuroid." Notably, external acoustic stimulation produced by the FS device affected the pressuroids. Furthermore, the pressuroids exhibited upregulation in mechanosensitive genes and proteins, PIEZO1/2. CyclinD1 and PCNA, which are strongly associated with cell adhesion and proliferation, were elevated by PIEZO1/2. In addition, we found that pressuroids significantly increase angiogenic paracrine factor secretion, promote cell adhesion molecule expression, and enhance M2 immune modulation of Thp1 cells. Altogether, we have concluded that our pressuroid would suggest a more effective therapy method for future cell therapy than the conventional one.
Light‐based therapy has been reported as a potential preconditioning strategy to induce intracellular reactive oxygen species (ROS) signaling and improve the angiogenic properties of various types of cells. However, bio‐stimulation mechanisms of light therapy in terms of ROS‐heat shock proteins (HSPs) mediated anti‐apoptotic and angiogenic pathways in human adult stem cells have not been fully delineated yet. Commonly used light sources such as light‐emitting diode (LED) and laser are accompanied by drawbacks, such as phototoxicity, thermal damage, and excessive ROS induction, so the role and clinical implications of light‐induced HSPs need to be investigated using a heat‐independent light source. Here, we introduced organic LED (OLED) at 610 nm wavelength as a new light source to prevent thermal effects from interfering with the expression of HSPs. Our results showed that light therapy using OLED significantly upregulated anti‐apoptotic and angiogenic factors in human bone marrow mesenchymal stem cells (hMSCs) at both gene and protein levels via the activation of HSP90α and HSP27, which were stimulated by ROS. In a mouse wound‐closing model, rapid recovery and improved re‐epithelization were observed in the light‐treated hMSCs transplant group. This study demonstrates that the upregulation of Akt (protein kinase B)‐nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling, caused by HSP90α and HSP27 expression, is the mechanism behind the anti‐apoptotic and angiogenic effects of OLED treatment on stem cells.
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