RESUMEN
Natural killer (NK) cell therapies, primarily based on chimeric antigen receptor NK cells (CAR-NK), have been developed and applied clinically for therapeutic treatment of patients with mid-to-late-stage tumors. However, NK cell therapy has limited efficacy due to insufficient antigen expression on the tumor cell surface. Here, a universal "illuminate tumor homogenization antigen properties" (ITHAP) strategy to achieve stable and controlled antigen expression on the surface of tumor cells using nanomedicine, thus significantly enhancing the immune recognizability of tumor cells, is described. The ITHAP strategy is used to generate bio-liposomes (Pt@PL-IgG) composed of intermingled platelet membranes and liposomes with NK-activatable target antigen (IgG antibodies) and cisplatin pre-drug. It is demonstrated that Pt@PL-IgG successfully targets tumor cells using the autonomous drive of platelet membranes and achieves IgG implantation on tumor cells by utilizing membrane fusion properties. Moreover, it is shown that the Pt-DNA complex combined with NK cell-induced pyroptosis causes substantial interferon (IFN) secretion, thus providing a synthase-stimulator of interferon genes (STING)-IFN-mediated positive immune microenvironment to further potentiate NK therapy. These results show that anchoring cancer cells with NK-activatable target antigens is a promising translational strategy for addressing therapeutic challenges in tumor heterogeneity.
Asunto(s)
Células Asesinas Naturales , Neoplasias , Liposomas/química , Células Asesinas Naturales/química , Células Asesinas Naturales/inmunología , Neoplasias/química , Neoplasias/inmunología , Antígenos de Neoplasias/química , Antígenos de Neoplasias/inmunología , Platino (Metal)/química , Humanos , Animales , Ratones , Línea Celular TumoralRESUMEN
Polyethylene (PE) products are widely used in daily life, agriculture, and industry because of their convenience and economic value. However, PE is one of the polymer materials remarkably resistant to degradation. Current methods of plastic waste disposal pose a threat to the environment and produce microplastic particles (MPP), which becomes a global environmental concern because of its accumulation. In this study, a PE-degrading fungus Aspergillus flavus named PEDX3, was isolated from the gut contents of wax moth Galleria mellonella. The results indicated that high-density polyethylene (HDPE) MPP was degraded into the MPP with a lower molecular weight by strain PEDX3 after 28 days incubation. In addition, Fourier Transform - Infrared Spectroscopy (FT-IR) results showed the appearance of carbonyl groups and ether groups of MPP, which also validated the degradation of PE. Furthermore, the potential degradation enzymes were investigated by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Finally, two laccase-like multicopper oxidases (LMCOs) genes, AFLA_006190 and AFLA_053930, displayed up-regulated expression during the degradation process, which may be the candidate PE-degrading enzymes. These results have demonstrated that the A. flavus strain PEDX3 has an ability to degrade microplastic particles and the two PE-degrading enzymes provide a promising application for the PE MPP remediation.