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Abstract: Traditional targeting approach utilizing biological ligands has to face the problems of limited receptors and tumor heterogeneity. Herein, a two‐step tumor‐targeting and therapy strategy based on inverse electron‐demand [4+2] Diels–Alder cycloaddition (iEDDA) is described. Owing to the unique acidic tumor microenvironment, an intravenous injection of tetrazine modified pH (low) insertion peptide could efficiently target and incorporate onto various cell surfaces in tumor tissue, such as cancer cells, vascular endothelial cells, and tumor‐associated fibroblasts. The “receptor‐like” tetrazine groups with a large amount and homogeneous intratumoral distribution could then serve as the baits to greatly amplify the tumor‐targeting ability of indocyanine green (ICG)‐loaded and trans‐cyclooctene (TCO)‐conjugated human serum albumin (HSA) nanoparticles (TCO‐HSA‐ICG NPs) via iEDDA after the second intravenous injection. Compared with the passive enhanced permeability and retention (EPR) effect and traditional active targeting approaches, the targeting performance and photothermal therapeutic effect based on the two‐step strategy are significantly enhanced, while no notable toxicity is observed. As acidity is a characteristic of solid tumor, the two‐step strategy can serve as a universal and promising modality for safe and high‐performance nanoparticle‐based antitumor therapy. [ABSTRACT FROM AUTHOR]

Abstract: It is difficult and significant to realize the aim of “one‐pot” and “nonenzyme” for traditional colorimetric detection of blood glucose. The synthesis of nanomaterials with 2D morphology is also a challenge for the bovine serum albumin (BSA)‐directed method. Here, the BSA‐directed synthesis avenue for metal oxide with 2D nanomorphology is developed. MnO2 nanoflakes (NFs) with controllable morphology can be obtained by changing the synthesis conditions. Fortunately, not only is the glucose oxidase (GOx)‐like nanozyme (MnO2 NFs) discovered, but MnO2 NFs also show dual enzyme activities (GOx‐like activity and peroxidase‐like activity) in similar pH range. That is to say, a “tandem nanozyme” (nanomaterial with tandem enzyme‐like characteristics) is presented here. Further, the one‐pot nonenzymatic strategy is proposed for the colorimetric detection of glucose, where the oxidation of glucose and the colorimetric detection of H2O2 are simultaneously conducted under the catalysis of the single nanozyme (MnO2 NFs). The method shows high sensitivity, low limit of detection, and short detection time, due to the proximity effect and in situ reaction. The as‐synthesized 2D tandem nanozyme expands the species of nanozymes, and the proposed strategy breaks traditional colorimetric detection process, accomplishing the purposes of “one‐pot” and “nonenzyme” in the true sense. [ABSTRACT FROM AUTHOR]