Abstract
We report the design and dual-modality evaluation of a precision-glycosylated, clickable human serum albumin (HSA) nanoplatform tailored to address the tumor microenvironment.
Background
Albumin’s circulating reservoir has long been used as a passive cargo for diagnostics and therapeutics. However, its uptake at the tumor border has been heterogeneous and difficult to attribute spatially.
Methods
We engineered a panel of glyco-HSA constructs with sialic-acid-presenting termini and a clickable handle. Tumor uptake was quantified with PET imaging and validated against spatial transcriptomics readouts.
Results
Tumor-to-liver ratio at 24h reached 1.9x baseline for the lead construct. Spatial transcriptomics confirmed co-localization with CD68+ tumor-associated macrophage signatures across two cohorts.
Conclusions
The platform supports a tunable, manufacturable approach to TME targeting. Next, we extend to immune-rewiring payloads.
