Fengli Qu

Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis

Clinical diagnosis of ovarian cancer lacks high accuracy due to the weak selection of specific biomarkers along with the circumstance biomarkers localization. Clustering analysis of proteins transported on exosomes enables a more precise screening of effective biomarkers. Herein, through bioinformatics analysis of ovarian cancer and exosome proteomes, two coexpressed proteins, EpCAM and CD24, specifically enriched, were identified, together with the development of an as-derived dual-aptamer targeted exosome-based strategy for ovarian cancer screening. In brief, a DNA ternary polymer with aptamers targeting EpCAM and CD24 was designed to present a logic gate reaction upon recognizing ovarian cancer exosomes, triggering a rolling circle amplification chemiluminescent signal. A dynamic detection range of 6 orders of magnitude was achieved by quantifying exosomes. Moreover, for clinical samples, this strategy could accurately differentiate exosomes from healthy persons, other cancer patients, and ovarian cancer patients, enabling promising

Cisplatin Promotes Immunosuppression in Ovarian Cancer by Enhancing miR‐181a‐5p‐Enriched Extracellular Vesicles to Drive Regulatory T Cell Differentiation

ABSTRACT Although cisplatin (CDDP) is widely employed in combination immunotherapy, no CDDP‐based regimen has shown a survival benefit when treating the ovarian cancers. This is mainly because the impact of CDDP on immunotherapy is not fully understood. A critical gap concerns how CDDP reshape the tumour microenvironment, especially through extracellular vesicles (EVs)‐mediated communication. In this work, using human and murine ovarian cancer cells as a model, we demonstrate that CDDP boosts the secretion of EVs from cancer cells, while exerting no such effect on non‐cancerous cells. These CDDP‐induced tumour‐derived EVs, in turn, drive the differentiation of CD4 + T cells towards immunosuppressive regulatory T cells (T reg cells), which are known to limit the efficacy of immunotherapy. Based on next‐generation sequencing, a significant enrichment of miR‐181a‐5p was identified in CDDP‐induced tumour‐derived EVs, and further functional studies confirmed that this microRNA promoted T reg cell differentiation via suppressing sirtuin 1 (SIRT1), a key regulator of the transcription factor forkhead box protein P3 (FOXP3). Importantly, inhibition of miR‐181a‐5p abrogated the T reg ‐promoting effect of CDDP‐induced tumour‐derived EVs, a finding further validated in vivo , where blockade of miR‐181a‐5p not only impaired T reg differentiation but also restored T‐cell‐mediated antitumour immunity and restrained tumour growth. Together, these findings uncover a previously unrecognised mechanism by which CDDP exacerbates immunosuppression via miR‐181a‐5p‐enriched EVs and suggest that targeting this pathway could improve the therapeutic efficacy of combination immunotherapy in ovarian cancer.