Bifunctional Nanoassembly Enables Metabolism-Driven Microfluidic Blood Screening Guided by MRI Localization for Cancer Monitoring

Early detection and precise tumor localization are critical for improving treatment outcomes and enabling more targeted and minimally invasive therapies as biotechnology evolves. However, endogenous biomarkers from early lesions face significant challenges, such as short circulation times and blood dilution, which hinder early diagnostic efforts. In this study, we present a multimodal nanosensor specifically engineered to target cancer by responding to CD44 and tumor-associated enzymes within the microenvironment. Following systemic administration, the nanosensor selectively accumulates at the disease site, delivering hexaminolevulinate (HAL) to produce protoporphyrin IX (PpIX) as a synthetic biomarker, thus amplifying disease signals for analysis via a microfluidics-based device. Concurrently, embedded Gd₂O₃ nanoclusters facilitate tumor visualization through magnetic resonance imaging (MRI). Beyond tumor diagnosis, this innovative methodology supports the multimodal monitoring of drug response through the assessment of blood reporter signals and MRI imaging. This multifunctional system addresses critical limitations in traditional cancer diagnostics, which typically rely on sequential blood biomarker tests, followed by imaging. Our approach enhances diagnostic efficiency, minimizes the need for invasive procedures, and promotes more accurate and personalized cancer care.