DNA nanodevice as a multi-module co-delivery platform for combination cancer immunotherapy.

A major challenge in combining cancer immunotherapy is the efficient delivery of multiple types of immunological stimulators to elicit a robust anti-tumor immune response and reprogram the immunosuppressive tumor microenvironment (TME). Here, we developed a DNA nanodevice that was generated by precisely assembling three types of immunological stimulators. The doxorubicin (Dox) component induced immunogenic cell death (ICD) in tumor cells and enhanced phagocytosis of antigen-presenting cells (APCs). Exogenous double-stranded DNA (dsDNA) could act as a molecular adjuvant to activate the stimulator of interferon genes (STING) signaling in APCs by engulfing dying tumor cells. Interleukin (IL)-12 and small hairpin programmed cell death-ligand 1 (shPD-L1) transcription templates were designed to regulate TME. Additionally, for targeted drug delivery, multiple cyclo[Arg-Gly-Asp-(d-Phe)-Cys] (cRGD) peptide units on DNA origami were employed. The incorporation of disulfide bonds allowed the release of multiple modules in response to intracellular glutathione (GSH) in tumors. The nanodevice promoted the infiltration of CD8+ and CD4+ cells into the tumor and generated a highly inflamed TME, thereby enhancing the effectiveness of cancer immunotherapy. Our research results indicate that the nanodevice we constructed can effectively inhibit tumor growth and prevent lung metastasis without obvious systemic toxicity, providing a promising strategy for cancer combination treatment.

Label-free proteomic analysis and functional analysis in patients with intrauterine adhesion.

Intrauterine adhesion (IUA) is one of the principal causes of secondary infertility in women of reproductive age, which seriously affects female reproductive function and quality of life. In recent years, the incidence of IUA has been increasing year by year, but its pathological mechanism has not yet been clarified. This study intended to reveal the pathogenesis of IUA and find new therapeutic targets by analyzing the proteomic differences between intrauterine adhesion tissues and normal human endometrial tissues. In the label-free quantitative proteomics, we identified 789 up-regulated differentially expressed proteins (DEPs) and 539 down-regulated DEPs. These DEPs were further analyzed by Gene Ontology (GO) annotation and enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis to preliminarily clarify the biomarkers involved in the pathogenesis of the IUA. The DEPs were further verified by parallel reaction monitoring (PRM) to confirm the results of proteomics. Finally, 7 target proteins may be candidates for treatment and elucidating the pathophysiology of IUA. SIGNIFICANCE: IUA is a fertility complication, which has increasing incidence recently. Until now, only a little research paid attention to the proteomic changes of IUA. This is the first study focused on the comparative analysis of endometrial tissue between IUA patients and normal women. We found 7 key proteins that may become the potential biomarkers of IUA.