Near‐Infrared‐Responsive Digital PCR‐Assisted Renal Cancer Exosomal miRNAs Insights and Regulation of Macrophage Polarization
Exosomes derived from tumors are critical agents in intercellular communication and the tumor microenvironment, offering a rich source of signatures for renal cell carcinoma (RCC) diagnosis. Conventional diagnostic techniques often suffer from limited sensitivity and can be invasive. This study presents an innovative approach using near-infrared (NIR) digital PCR (dPCR) with black phosphorus-embedded gelatin microcarriers for profiling exosomal miRNAs and modulating STAT3 signaling and macrophage polarization. Microcarriers produced via microfluidics, characterized by their phase-change and photothermal properties, are subjected to thermal cycling using a custom NIR source. The study identified a 4.2-fold increase in miR-210 levels in RCC cells (ACHN and A498) compared to normal cells (HK-2), with miR-126 and miR-30c levels decreasing by 7-9 times. Additionally, the method achieved a 20-fold enrichment of miRNA-34 in exosomes, leading to reduced STAT3 expression and decreased M2 macrophage polarization after co-incubation. This pioneering dPCR method provides a robust tool for early RCC detection through exosomal miRNA profiling and opens new avenues for therapeutic exosome engineering. The study underscores the potential of dPCR-based exosome genotyping in identifying cancer biomarkers and developing novel treatment strategies.
Authors
- Dingmeng Hu
- Fangfu Ye (ORCID: https://orcid.org/0000-0003-1279-105X)
- Lexiang Zhang (ORCID: https://orcid.org/0000-0003-0374-4382)
- Rokshana Parvin (ORCID: https://orcid.org/0000-0002-2558-2735)
- Bing Han (ORCID: https://orcid.org/0000-0003-4584-1092)
- Dexuan Wang (ORCID: https://orcid.org/0000-0002-0261-4749)
- Peiyu Chen (ORCID: https://orcid.org/0000-0003-0693-2776)
- Lin Ke (ORCID: https://orcid.org/0009-0000-6189-6611)
- Ganggang Wang
- Yun Cheng (ORCID: https://orcid.org/0000-0001-6497-4590)
- Siyue Lin
- Gen Yang (ORCID: https://orcid.org/0000-0002-0695-5583)
Institutions
- King University (US)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University (CN)
- Zhejiang Lab (CN)
- Institute of Physics (CN)
- University of Chinese Academy of Sciences (CN)
- State Key Laboratory of Nuclear Physics and Technology
- Columbia University (US)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1002/advs.202509407
- Citations
- 2
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Wenzhou Municipal Science and Technology Bureau
- University of Chinese Academy of Sciences
- National Key Research and Development Program of China
- Wenzhou Institute of Biomaterials and Engineering
- Science and Technology Plan Project of Wenzhou, China
- Natural Science Foundation of Zhejiang Province