Ultrabright near-infrared fluorescent DNA frameworks for near-single-cell cancer imaging

Cancer imaging approaching single-cell levels is highly desirable for studying in vivo cell migration and cancer metastasis. However, current imaging probes struggle to simultaneously achieve high sensitivity, deep-tissue penetration and tissue specificity. Here we report size- and shape-resolved fluorescent DNA framework (FDF) dots with tail emission in the second near-infrared window (1,000–1,700 nm, NIR-II), which enable near-single-cell-level, tumour-targeting deep-tissue (~1 cm) NIR-II imaging in tumour-bearing mouse models. The construction of DNA frameworks with embedded hydrophobic nanocavity results in the non-covalent encapsulation of a designed NIR-Ib (900–1,000 nm) probe (dye Sq964). The FDF dots exhibit high water solubility, brightness and photostability. We find that the stable tumour retention of FDF dots with enhanced signal intensity arises from their shape-dependent accumulation in tumour cells. FDF-dot-based cancer imaging reveals in vivo sensitivity down to ~40 tumour cells, high tumour-to-normal tissue ratios up to ~26 and long-term imaging over 11 days. We also demonstrate NIR-II-image-guided breast cancer surgery with the complete excision of metastases with a minimum size of ~53 μm (~20 cells).