Conventional plasmonic nanogap assemblies face a major challenge in biological applications due to their lack of cellular specificity, often leading to off-tumor assembly and false signals in normal cells. To overcome this limitation, we developed an endogenous dual-input-activated strategy for spatially confined intracellular in situ self-assembly of a gold nanoprism (Au NPR) trimer-based plasmonic nanogap. This dual-input-triggered assembly mechanism ensures spatially controlled formation of Au NPR trimers exclusively within target tumor cells, thereby facilitating high-contrast delineation of the tumor/normal boundary with minimal off-tumor background. The in situ assembled Au NPR trimers generate strong electromagnetic hot spots, enabling plasmon-enhanced fluorescence (PEF) with a signal amplification of up to 19.6-fold and an 8.3-fold improvement in the tumor-to-normal cell discrimination ratio, facilitating high-contrast molecular imaging and precise delineation of tumor boundaries. By integrating an endogenous dual-biomarker-activated strategy with programmable DNA assembly, this work provides a robust, generalizable platform for high-contrast delineation of the tumor/normal boundary and sets a new paradigm for the development of smart tumor-specific nanotechnologies.
Xu et al. (Wed,) studied this question.