Exosomes derived from heat-stressed tumour cells (HS-TEXs), which contain abundant heat shock protein (HSP) 70, strongly induce antitumour immune responses. HSP70-induced interleukin (IL)-6 promotes IL-17 expression and causes rejection of established prostate tumours. However, it remains unclear whether HS-TEXs exhibit antitumour effects by converting regulatory T cells (T ) into T helper type 17 (Th17) cells. In this study, we found that compared with TEXs, HS-TEXs were more potent in stimulating secretion of IL-6 from dendritic cells. In vitro, IL-6 blocked tumour cell-derived transforming growth factor beta 1-induced T differentiation and promoted Th17 cell differentiation. HS-TEXs exerted strong antitumour effects, converting T into Th17 cells with high efficiency, a process that was entirely dependent upon IL-6. Neutralization of IL-17 completely abolished the antitumour effect of TEXs, but only partially inhibited that of HS-TEXs. In addition, we found higher levels of IL-6 and IL-17 in serum from tumour patients treated with hyperthermia, and an increase in Th17 cells and a decrease in T was detected in peripheral blood mononuclear cells isolated from these patients after hyperthermia. Therefore, our results demonstrate that HS-TEXs possess a powerful capacity to convert immunosuppressive T into Th17 cells via IL-6, which contributes to their potent antitumour effect.
Disruption and vasoconstriction of the blood vessels that results in tissue hypoxia can retard the wound healing process. Transcutaneous oxygen delivery for the hypoxic tissue has been shown to be an effective method for enhanced wound regeneration, for example, hyperbaric oxygen therapy and topical oxygen therapy. However, these techniques' clinical applications are limited by high cost and complicated protocols. To combat this, a bioactive living hydrogel based on photosynthetic microorganisms is designed for enhanced wound healing by production and local delivery of oxygen to alleviate acute and chronic tissue hypoxia. Spirulina platensis (SP), a type of photosynthetic bacteria is coated with the natural polymer carboxymethyl chitosan to obtain the SP gel, which keeps the oxygen generation capability of the SP while promoting its adhesion to the infected wound. Moreover, chlorophyll, a natural photosensitizer, is released from the SP irradiated with 650‐nm laser, and generates reactive oxygen species, thereby causing photodynamic destruction of bacteria in the infectious area. Cytotoxicity assays and in vivo toxicity assessment demonstrate the excellent biocompatibility of the gel. The SP gel is easy to obtain, cheap for mass production, and convenient for usage, which is promising for clinical application.
How the tumor microenvironment educates dendritic cells (DCs) to promote tumorigenesis remains largely unknown, and the role of tumor-derived exosomes (TEXs) in tumorigenesis is controversial. Here, we report that in addition to the activation of DCs, TEXs induce DCs to produce increased interleukin-6 (IL-6), which dramatically promotes tumor invasion by increasing signal transducer and activator of transcription 3 (STAT3)-dependent matrix metalloproteinases 9 transcription activity in tumor cells. HSP72 and HSP105 on the TEX surface induce IL-6 secretion of DCs in a TLR2- and TLR4-dependent manner. In addition, HSP72 and HSP105 are predominantly present on exosomes from sera of tumor patients but not healthy people, indicating their value in tumor prediction. Furthermore, TEXs are powerful activators of DCs, and the depletion of IL-6 converts TEXs from tumor promoters to tumor inhibitors . Therefore, our results reveal a novel mechanism for the TEX-mediated education of DCs and shed light on the conundrum that TEXs present by playing dual roles in tumorigenesis.
Rationale: Chronic wounds are one of the common complications of diabetes. Due to the physiological conditions of diabetic patients, these wounds are more susceptible to bacterial infections and the formation of bacterial biofilms, leading to the inefficiency of conventional antibiotic treatment. Methods: Here, hollow mesoporous silica nanoparticles (HMSN) were used as the nanocarriers for co-delivery of azithromycin (AZM) and glucose oxidase (GOX), achieving a remarkable synergistic effect in chronic diabetic wounds. GOX possesses the catalytic ability to consume glucose and produce H 2 O 2 in the diabetic wound area. The down-regulation of local glucose could effectively improve the chronic diabetic wound microenvironment. Meanwhile, the generated H 2 O 2 effectively inhibits bacterial growth and eradicates bacterial biofilms with the synergism of antibiotics AZM. Results: In the bacteria-infected diabetic cutaneous wound models, the reduction of glucose, generation of H 2 O 2 , and release of AZM could effectively reduce the bacterial infection and promote the wounds healing. Moreover, there is no obvious toxicity behavior after the treatment. Conclusions: Therefore, the designed nanosystem could effectively accelerate the diabetic wound healing process by the amelioration of the hyperglycemia microenvironment and the eradication of bacterial biofilms around the wounds, making them promising candidates for clinical transformation.
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