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Abstract PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin‐proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano‐PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano‐PROTACs are developed by encapsulating PROTACs in glutathione (GSH)‐responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano‐PROTAC, nanoengineered BRD4 degrader ARV‐771, improves BRD4 protein degradation and decreases the downstream oncogene c‐Myc expression. Benefiting from the GSH‐scavenging ability to amply the c‐Myc‐related ferroptosis and cell cycle arrest, this ARV@PDSA Nano‐PROTACs strategy shows superior anti‐tumor efficacy with a low dose administration and good biocompatibility in vivo. The findings reveal the potential of the Nano‐PROTACs strategy to treat a broad range of diseases by dismantling associated pathogenic proteins.

Abstract In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a “chemical factory” including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well‐fitness of nanomaterials for disease and satisfactory therapeutic effect.

Abstract Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (125I) are used in situ to construct active sites in a nanocatalyst (TiO2) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT). The obtained 125I‐TiO2 nanoparticles first construct superficial Ti3+ active sites via the reaction between Ti4+ and AEs. Then Ti3+ stretches and weakens the OH bond of the absorbed H2O, thus enhancing the radiolysis of H2O molecules and generating hydroxyl radicals (•OH). All in vitro and in vivo results demonstrate a good CIRT performance. These findings will broaden the application of radionuclides and introduce new perspectives to nanomedicine.