2. Academic Validation
  3. Antibody-DNA nanostructure conjugates exhibit inhibited effects on CT26 cells and prevent upregulation of PD-1 in the tumor microenvironment

Antibody-DNA nanostructure conjugates exhibit inhibited effects on CT26 cells and prevent upregulation of PD-1 in the tumor microenvironment

  • Int J Biol Macromol. 2025 Oct 3;330(Pt 3):148101. doi: 10.1016/j.ijbiomac.2025.148101.
Chengxun Li 1,  Fei Chen 2,  Jianing Wu 3,  Jun Ren 3,  Yingzhu Li 3,  Shengjie Li 4,  Zuguang Xia 5
Affiliations

Affiliations

  • 1 Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200030, China.
  • 2 Department of General Surgery, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 3 Department of Clinical Laboratory, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • 4 Department of Clinical Laboratory, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: [email protected].
  • 5 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200030, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: [email protected].
PMID: 41046886 DOI: 10.1016/j.ijbiomac.2025.148101
Abstract

Antibody drug conjugates (ADCs) offer targeted Cancer therapy but face limitations in drug loading, stability, and immune modulation. Here, antibody DNA nanostructure conjugates (ADNCs) is reported as a next-generation platform that overcomes these challenges. By leveraging the programmable architecture of DNA nanostructures, ADNCs achieve high, tunable drug payloads without inducing antibody aggregation-a major drawback of conventional ADCs. In CT26 cells, gemcitabine-loaded ADNCs trigger dual cell death pathways-caspase-3-mediated Apoptosis and RIP3-mediated necroptosis-enhancing tumor cell killing. In the CT26 syngeneic model, ADNCs suppress tumor growth with no observable toxicity and, notably, activate anti-tumor immunity without upregulating PD-1, suggesting avoidance of T-cell exhaustion. Critically, ADNCs maintain efficacy in patient-derived xenograft (PDX) models despite tumor heterogeneity. The study presents a novel, stable, and scalable antibody-drug conjugate (ADC)-inspired platform that integrates high payload delivery capacity with enhanced and adjustable drug-loading capabilities-characteristics that are seldom achieved in existing ADC technologies-thereby demonstrating translational potential for applications in precision oncology.

Keywords

Antibody drug conjugate; Colorectal cancer; Gemcitabine; Tumor microenvironment.

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