한빛사
>
한빛사논문
한빛사논문
- 조회143
J. Clin. Invest., Mar 11 2025, e184964 | https://doi.org/10.1172/JCI184964
Tumor-specific surface marker-independent targeting of tumors through nanotechnology and bioorthogonal glycochemistry
Hyesun Hyun1, Bo Sun2, Mostafa Yazdimamaghani1, Albert Wielgus1, Yue Wang3, Stephanie Ann Montgomery1,4,5, Tian Zhang6, Jianjun Cheng7, Jonathan S Serody1,8,9*, and Andrew Z. Wang10*
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
2College of Pharmacy, Skaggs Pharmaceutical Sciences Center, University of Arizona; Tucson, AZ, USA
3Department of Pharmacology, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
4Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
5Division of Comparative Medicine, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
6Department of Medicine and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center; Dallas, TX, USA
7School of Engineering, Westlake University; Hangzhou, Zhejiang, China
8Department of Medicine, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
9Department of Immunology and Microbiology, University of North Carolina at Chapel Hill; Chapel Hill, NC
10Department of Radiation Oncology, University of Texas Southwestern Medical Center; Dallas, TX, USA
JSS and AZW are co-corresponding authors.
*Corresponding authors: Andrew Z. Wang, Jonathan S Serody
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
2College of Pharmacy, Skaggs Pharmaceutical Sciences Center, University of Arizona; Tucson, AZ, USA
3Department of Pharmacology, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
4Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
5Division of Comparative Medicine, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
6Department of Medicine and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center; Dallas, TX, USA
7School of Engineering, Westlake University; Hangzhou, Zhejiang, China
8Department of Medicine, University of North Carolina at Chapel Hill; Chapel Hill, NC, USA
9Department of Immunology and Microbiology, University of North Carolina at Chapel Hill; Chapel Hill, NC
10Department of Radiation Oncology, University of Texas Southwestern Medical Center; Dallas, TX, USA
JSS and AZW are co-corresponding authors.
*Corresponding authors: Andrew Z. Wang, Jonathan S Serody
Abstract
Biological targeting is crucial for effective cancer treatment with reduced toxicity but is limited by the availability of tumor surface markers. To overcome this, we developed a nanoparticle-based, Tumor-specific suRfACE maRker-independent (TRACER) targeting approach. Utilizing the unique biodistribution properties of nanoparticles, we encapsulated Ac4ManNAz to selectively label tumors with azide reactive groups. Surprisingly, while NP-delivered Ac4ManNAz was cleared by the liver, it did not label macrophages, potentially reducing off-target effects. To exploit this tumor-specific labeling, we functionalized anti-4-1BB antibodies with dibenzocyclooctyne (DBCO) to target azide-labeled tumor cells and activate the immune response. In syngeneic B16F10 melanoma and orthotopic 4T1 breast cancer models, TRACER enhanced anti-4-1BB's therapeutic efficacy, increasing median survival time. Immunofluorescence analyses revealed increased tumor infiltration of CD8+ T and NK cells with TRACER. Importantly, TRACER reduced hepatotoxicity associated with anti-4-1BB, resulting in normal serum ALT and AST levels and decreased CD8+ T cell infiltration in the liver. Quantitative analysis confirmed a 4.5-fold higher tumor-to-liver ratio of anti-4-1BB accumulation with TRACER compared to conventional anti-4-1BB antibodies. Our work provides a promising approach for developing targeted cancer therapies that circumvent limitations imposed by the paucity of tumor-specific markers, potentially improving efficacy and reducing off-target effects to overcome liver toxicity associated with anti-4-1BB.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-18)
- 국외 연구진
- 바이오·의료융합 > 바이오·의료융합 기타
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
