Quantification of cyclic DNA polymerization with lanthanide coordination nanomaterials for liquid biopsy

Quantification of circulating tumor DNA (ctDNA) is of great importance in liquid biopsy but difficult due to its low amount in bodily fluids. To meet this high demand, a novel method for ctDNA detection is established by quantifying cyclic DNA polymerization using lanthanide coordination polymers (Ln-CPs). Relying on the coordination between the pyrophosphate ion (PPi) and trivalent cerium ion (Ce³⁺), organic ligand-free PPi-Ce coordination polymer networks (PPi-Ce CPNs) with enhanced fluorescence are prepared for the first time. By surveying the optical properties of PPi-Ce CPNs, it is found that PPi regulates electric-dipole transition of Ce³⁺ to the lowest excited state, thus facilitating the emission of fluorescence. Therefore, fluorescence enhancement of PPi-Ce CPNs originates from the ligand field effect rather than the normal antenna effect. Moreover, a new strategy to quantify DNA polymerization is developed based on PPi-Ce CPNs. By introducing multifold cyclic DNA polymerization, a small amount of ctDNA triggers the exponential generation of PPi to form plenty of PPi-Ce CPNs. Accordingly, a biosensor is constructed for sensitive ctDNA detection by measuring the intense fluorescence of PPi-Ce CPNs. The biosensor is capable of sensing ctDNA at the sub-femtomolar level, which is far better than the analytical performances of commercial dyes. Besides, the analytical method is able to detect single nucleotide polymorphism and determine ctDNA in real samples. Considering that DNA polymerization is widely used in bio-recognition, bio-assembly and biomineralization, the work provides a versatile quantitative strategy of making relevant processes precise and controllable.