Abstract Introduction: Extracellular Vesicles (EVs) carry tumor-derived biomolecules and represent a promising source for liquid biopsy-based cancer detection. Many recent studies have revealed critical biomarkers from plasma EV, establish potential diagnostic targets for pancreatic cancers, ovarian cancers and other hard-to-diagnose cancers1. Unlike circulating free DNA (cfDNA) or soluble proteins, EVs are actively secreted by viable tumor cells and encapsulate proteins, nucleic acids, and lipids within a protective bilayer that preserves molecular integrity. This stability and cell specificity make EVs ideal for minimally invasive disease monitoring. However, plasma EV isolation remains challenged by abundant protein contaminants that compromise downstream molecular analysis. A simple, high-purity, automation-compatible isolation method is essential to improve EV-based biomarker profiling, particularly from heterogeneous blood derived samples. Methods: A lipid nanoprobe (LNP)-based magnetic bead system (Captis Diagnostics Inc) was optimized for rapid, high-specificity enrichment of plasma EVs 2. EVs post enrichment were assessed by cargo DNA, RNA and core tetraspanin abundance compared with pre-enrichment samples. Depletion of albumin and lipoprotein contaminants were confirmed by immunoassays. Comparative recovery efficiency and purity metrics were benchmarked against leading commercial EV isolation reagents. To assess broad biomarker compatibility, EVs from multiple cancer cell lines were spiked into healthy plasma and isolated using LNP beads. Enriched EVs were analyzed using OriGene multiplexed immunoassay panels covering cancer-relevant protein classes, including adhesion molecules, oncogenic receptors, and immune-modulatory factors. These markers represent key tumor hallmarks such as invasion, migration, immune evasion, and therapeutic resistance—commonly represented in EVs from solid tumors. Results: LNP-based EV enrichment achieved very high EV recovery (85%) with substantially reduced albumin and lipoprotein carryover compared with benchmark reagents. The immunoassay panels demonstrated robust detection of key cancer-associated biomarkers across diverse cell-line-derived EVs. The results demonstrating strong EV-specific signals and substantial reduction of nonspecific background These findings indicate that LNP isolation provides superior purity and robust compatibility with downstream quantitative analyses. Conclusion: LNP-mediated EV enrichment provides a rapid, high-purity, and sample-efficient platform for capturing cancer-derived biomarkers directly from plasma. When integrated with omic-assays, this approach enables broad phenotypic characterization of tumor-derived EVs and supports development of minimally invasive diagnostic and treatment-monitoring strategies. Citation Format: Qiuyan Ma, Dehe Kong, Sidhant Narula, Jin-Qiu (Jessie) Chen. Lipid nanoprobe magnetic beads enable high-purity plasma EV isolation for broad-spectrum cancer biomarker detection abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3362.
Ma et al. (Fri,) studied this question.
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