Persistent luminescence (PersL) nanoparticles (PLNPs) with excitation-afterglow emission separation character, have brought luciferous prospect for ultrasensitive optical detection to circumvent the weakness of clinical fluorescence modality, benefiting from the strengths of autofluorescence-free, low phototoxicity and superior photostability. Nevertheless, small dimensions of PLNPs (<200 nm, suitable for in vivo diagnosis) synthesized via current procedures are inevitably accompanied with PersL brightness sacrifice. Whereas the past few years have witnessed advances to promote the performance of nanophosphor, proposing a versatile and sustainable approach to boost the excitation absorption capacity, thus amplifying the PersL is of industrywide urgency. Here, we first report a "lanthanide-chelate sensitization" strategy involving Eu-DOTA as strong photon harvester and Zn2SnO4: Cr3+, Eu3+ (ZSCE) PLNPs as matched acceptor to steadily augment the intensity of obtained ZDE PLNPs via efficacious Fo & BULL;rster-type energy transfer. Photobleaching resistant ZDE PLNPs with different DOTA-Eu substitutions enable maximal 3.9-fold luminous brightness and 1.4-fold decay lifetime over bare PLNPs. Cladded with hyaluronic acid (HA), ZDE@HA PLNPs performed high signal-to-noise ratio imaging and accurate tumors boundary depicting which facilitates PersL-guided breast tumors excision. Strikingly, the "Ln-chelate sensitization" concept could serve as an extensible approach to optimize existing PLNPs, which lightens up new perspectives for ultra-contrastive malignancy navigation.