Tumor-specific surface marker-independent targeting of tumors through nanotechnology and bioorthogonal glycochemistry.

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 (NP-based), tumor-specific surface marker-independent (TRACER) targeting approach. Utilizing the unique biodistribution properties of NPs, we encapsulated Ac4ManNAz (Maz) to selectively label tumors with azide-reactive groups. Surprisingly, while NP-delivered Maz 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 Abs with dibenzocyclooctyne to target azide-labeled tumor cells and activate the immune response. In syngeneic B16F10 melanoma and orthotopic 4T1 breast cancer models, TRA

SUBMITTER: Hyun H 

PROVIDER: S-EPMC12043094 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature