In biological samples, numerous substances are present, some of which may interfere with the adsorption and hybridization-triggered release of FAM-ssDNA, leading to false signals. Thus, it is essential that the FAM-ssDNA can adsorb to DFNS@DA particles and be released only when exposed to target cDNA. ssDNA of different lengths and mismatch sequences were first selected to verify the selectivity of the FAM-ssDNA/DFNS@DA system. As shown in Fig. , all the non-target ssDNA produced very weak signal (Fig. ). Furthermore, we evaluated the interference of some representative proteins including Mb (16 kDa, 2.1 × 3.5 × 4.4 nm), OVA (42.7 kDa, 7 × 4.5 × 5 nm), and HSA (66 kDa, 12 × 4 × 4 nm). Fig. shows that the proteins produced some weak fluorescence signal, with Mb giving the same signal between DFNS-4@DA and DFNS-20@DA particles. Both OVA and HSA produced weaker signal on DFNS-4@DA than DFNS-20@DA, most probably due to the smaller pores in DFNS-4@DA, which prevented the large proteins from entering the nanochannels of the DFNS. Therefore, DFNS-4@DA compared more favourably than DFNS-20@DA for resisting protein-induced dissociation of the ssDNA probe. The selectivity of FAM-ssDNA/DFNS@DA complex for miR-21 detection was further confirmed using five common miRNAs as references: miR-122, miR-143, miR-let-7a, miR-let-7e and miR-144.