Noninvasive Assessment of Protease Activity in Osteosarcoma via Click Chemistry‐Mediated Enrichment of Extracellular Vesicles
Abstract Osteosarcoma (OS), the most common bone cancer in children, is characterized by aggressive tumors and subclinical metastasis. Metastasis significantly impacts OS patient survival rate, highlighting the need for frequent assessment of disease progression and treatment response. The study introduces OS extracellular vesicles (EV) matrix metalloproteinase (MMP) Activity Assay, noninvasively analyzing six combinations of OS EV surface markers and OS‐associated MMPs to generate a unique OS EV MMP profile for each patient. An OS EV MMP Activity Score is established from logistic regression of three top‐performing combinations to specifically distinguish metastatic OS from localized OS, achieving an area under the receiver operating characteristic (AUROC) curve of 0.97. The Scores from longitudinal monitoring of six OS patients strongly correlate with disease progression and treatment response, as confirmed by radiographic imaging. The OS EV MMP Activity Assay enables noninvasive and timely monitoring of disease progression and treatment response during the critical disease window of progression to metastatic OS, enhancing clinical management for OS patients.
Authors
- Noah Federman (ORCID: https://orcid.org/0000-0002-2627-6772)
- Hadar Keren‐Gill
- Hsiao‐hua Yu (ORCID: https://orcid.org/0000-0002-3603-6932)
- Audrey Qian
- Kim Chi Vo (ORCID: https://orcid.org/0000-0001-5581-1642)
- Steven J. Jonas (ORCID: https://orcid.org/0000-0002-8111-0249)
- Alice Soragni (ORCID: https://orcid.org/0000-0002-6634-2885)
- Hyo Yong Kim (ORCID: https://orcid.org/0000-0002-8931-8298)
- Hui Kong (ORCID: https://orcid.org/0000-0002-1382-7985)
- Jia‐Wei She
- Yazhen Zhu (ORCID: https://orcid.org/0000-0002-2130-8085)
- Sungyong You (ORCID: https://orcid.org/0000-0003-3513-1783)
- You‐Ren Ji (ORCID: https://orcid.org/0000-0001-6394-041X)
- Hsian‐Rong Tseng (ORCID: https://orcid.org/0000-0003-0942-5905)
- Sarah Dry (ORCID: https://orcid.org/0000-0002-1858-5225)
- Hans David Ulmert
- Ryan Zhang
- Joseph G. Crompton (ORCID: https://orcid.org/0000-0001-9325-2909)
- Jina Kim (ORCID: https://orcid.org/0000-0002-7662-6777)
- Yong Ju (ORCID: https://orcid.org/0000-0001-9550-4866)
- Junseok Lee (ORCID: https://orcid.org/0000-0002-3709-1386)
- Shaohua Lu
- Chen Zhao (ORCID: https://orcid.org/0000-0003-1324-1375)
- Aaron Phung
- Yusef Mathkour
- Daniel Gonzalez (ORCID: https://orcid.org/0000-0002-6530-2355)
Institutions
- Cedars-Sinai Medical Center (US)
- California NanoSystems Institute (US)
- Sun Yat-sen University (CN)
- University of California, Los Angeles (US)
- Fudan University (CN)
- Zhongshan Hospital (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Broad Center (US)
- Institute of Chemistry, Academia Sinica (TW)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1002/adfm.202422469
- Citations
- 4
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Institutes of Health
- Hyundai Hope On Wheels
- California NanoSystems Institute