Cancer chemotherapeutic drugs such as doxorubicin, mitomycin C, and gemcitabine, which are mostly small synthetic molecules, are still clinically useful for cancer treatment. However, despite considerable therapeutic efficacy, severe toxicity-associated problems, which are mainly caused by the non-specific mode of action such as chromosomal DNA damage and interference in the DNA replication even in normal cells, remain unresolved and a major challenge for safer and thus more widespread adoption of chemotherapy. Herein, an innovative platform is developed through beneficially integrating core peptide units into highly-ordered, stable, and flexibly guest-adaptable structure of apoferritin, which simultaneously fulfills high-capacity loading of chemotherapeutic drugs compared with the case of FDA-approved antibody-drug conjugates, efficient drug targeting to cancer cells, and cancer cell-specific drug release and activation. This approach dramatically reduces drug toxicity to normal cells, significantly enhances efficacy in in vivo cancer treatment without toxicity to normal organs of mice, and thus is expected to open up a novel clinical route to break through the limits of current cancer chemotherapy.

Although a variety of urinary cancer markers are available for in vitro diagnosis, inherent problems of urine environment—containing various inorganic/organic ions/molecules that vary in concentration over a 20‐fold range or more and significantly attenuate antibody avidity for markers—render conventional immunoassays unsuitable, remaining unresolved and a major challenge. Here we developed a 3D‐plus‐3D (3p3) immunoassay method, based on a single‐step urinary marker detection by 3D‐antibody probes, which are free of steric hindrance and capable of omnidirectional capture of markers in a 3D solution. The 3p3 immunoassay showed an excellent performance in the diagnosis of prostate cancer (PCa) through detecting PCa‐specific urinary engrailed‐2 protein, demonstrating 100% sensitivity and 100% specificity with the urine specimens of PCa‐related and other related disease patients and healthy individuals. This innovative approach holds a great potential in opening up a novel clinical route for precise in vitro cancer diagnosis and also pushing urine immunoassay closer to more widespread adoption.

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Cancer Chemotherapy In article number 2200765 by Jeewon Lee and co‐workers, optimized structures to enable cancer cell‐specific activation of chemotherapeutic drugs are constructed through integrating core peptide units into highly‐ordered, stable, and guest‐adaptable structures of human heavy chain ferritin (huHF) scaffolds. After endocytosis to cancer and normal cells, the drugs are released from huHF‐drug conjugates in cancer cells, whereas in normal cells, the huHF‐drug conjugates remain inactive without drug release.