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The accurate therapeutic evaluation for chronic myeloid leukemia (CML) drug is of great importance to minimize side effects and enhance efficacy. Herein, a facile and precise surface-enhanced scattering (SERS) approach based on coupled plasmonic field has been introduced to evaluate the therapeutic outcomes of antileukemia drug through ultrasensitive assay of caspase-3 activity in apoptotic cells. Caspase-3 as an apoptosis indicator could specifically cleave the N-terminus of biotinylated DEVD-peptide (biotin-Gly-Asp-Gly-Asp-Glu-Val-Asp-Gly-Cys) immobilized on the Au nanoparticle-decorated TiO 2 nanotube arrays (TiO 2 /Au NTAs) substrate. After the enzyme cleavage with caspase-3, Raman-labelled Au nanostar (AuNS) probes captured the residual DEVD-peptides via the recognition between streptavidin and biotin, thus resulting in an enhanced Raman response on the SERS platform. The variation of Raman intensity revealed caspase-3 activity that reflected the chemotherapeutic effect. On this platform, AuNS nanoprobes offered a large number of binding sites and intrinsic “hot spots” for Raman reporters, while TiO 2 /Au NTAs rendered a homogenously coupled electromagnetic field between the adjacent repeated units over the large area. In particular, a spatially expanding plasmonic field formed by coupling AuNSs with TiO 2 /Au NTAs would further heighten Raman enhancement. Taking these advantages, the strong and uniform Raman signals were achieved. Furthermore, the practicability investigation witnessed that the proposed SERS strategy was available to evaluate the therapeutic effect of dasatinib on CML K562 cells. The developed method possesses fascinating advantages of cost-effectiveness, excellent reproducibility and high sensitivity, which endows it with promising potential in apoptosis monitoring and anticancer drug development. [ABSTRACT FROM AUTHOR]