Investigator
Professor · Hunan University, Chemistry
A Membrane-Retained DNA Aptamer Promotes Intracellular Platinum Accumulation and Chemosensitization in Ovarian Cancer
Cisplatin resistance remains a major obstacle in the effective treatment of ovarian cancer. Here, we report a membrane-retained DNA aptamer, DR-A2, discovered via Cell-SELEX using cisplatin-resistant ovarian cancer cells as the selection target. DR-A2 exhibited high affinity and specificity toward drug-resistant ovarian cancer cells and their secreted exosomes, while showing negligible binding to drug-sensitive parental cells or normal epithelial cells. Mechanistic studies revealed that DR-A2 increases intracellular cisplatin retention in resistant cells. In vivo, DR-A2 preferentially accumulated in cisplatin-resistant xenografts and significantly boosted the antitumor efficacy of cisplatin without causing systemic toxicity. These results validate DR-A2 as a bifunctional aptamer capable of both selective tumor recognition and chemosensitization, offering a promising strategy to overcome platinum resistance in ovarian cancer.
Personalized Cancer-Specific Protein-Aptamer Corona for Orthogonal Multiplex Cancer Diagnosis
Aptamers are powerful synthetic recognition elements for biosensing, yet their application in complex biofluids, such as human serum, is critically limited by enzymatic degradation. To overcome this fundamental challenge, we introduce a novel analytical platform centered on the concept of a personalized protein-aptamer corona (PAC). This strategy leverages the spontaneous formation of a disease-specific protein corona on magnetic nanoparticles, which not only enriches low-abundance biomarkers but also creates a stabilized, nuclease-free nanobio interface for subsequent aptamer recognition. The integration of this PAC concept with an 8-channel orthogonal multiplexed electrochemical (OMEC) chip enables sensitive, amplification-free (PCR-free) signal transduction via alternating current voltammetry. By coupling this platform with machine learning algorithms, we translate complex, multiplexed aptamer binding signatures into a robust diagnostic output. Clinical validation on two independent cancer cohorts demonstrated outstanding performance, achieving an area under the curve of 99.50% for ovarian cancer (
An Aptamer‐Based Nanoflow Cytometry Method for the Molecular Detection and Classification of Ovarian Cancers through Profiling of Tumor Markers on Small Extracellular Vesicles
AbstractMolecular profiling of protein markers on small extracellular vesicles (sEVs) is a promising strategy for the precise detection and classification of ovarian cancers. However, this strategy is challenging owing to the lack of simple and practical detection methods. In this work, using an aptamer‐based nanoflow cytometry (nFCM) detection strategy, a simple and rapid method for the molecular profiling of multiple protein markers on sEVs was developed. The protein markers can be easily labeled with aptamer probes and then rapidly profiled by nFCM. Seven cancer‐associated protein markers, including CA125, STIP1, CD24, EpCAM, EGFR, MUC1, and HER2, on plasma sEVs were profiled for the molecular detection and classification of ovarian cancers. Profiling these seven protein markers enabled the precise detection of ovarian cancer with a high accuracy of 94.2 %. In addition, combined with machine learning algorithms, such as linear discriminant analysis (LDA) and random forest (RF), the molecular classifications of ovarian cancer cell lines and subtypes were achieved with overall accuracies of 82.9 % and 55.4 %, respectively. Therefore, this simple, rapid, and non‐invasive method exhibited considerable potential for the auxiliary diagnosis and molecular classification of ovarian cancers in clinical practice.
Professor
Hunan University · Chemistry