This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: After taking a pill, the drugs it contains are distributed throughout the body, reaching the tissues and cells affected by disease and performing their intended function. However, they also enter healthy cells, where they often cause more harm than good.
In a study published in the journal Nature Communications, a multidisciplinary team led by TUDa professors Felix Hausch from the Department of Chemistry and Alexander Loewer from the Department of Biology has shown how proteins occurring naturally in human cells can be used to target therapeutics specifically at diseased cells. Crucial to directing the active substances to disease-relevant cells was the development of small chemical compounds that can bind disease-associated proteins to natural proteins present in those cells, thereby blocking the disease-associated proteins. "We identified such molecules by Lego-like high-throughput conjugation chemistry," explains Min Zheng from the Structure-Based Drug Research Group at TU Darmstadt, who played a key role in the project as a chemist.
But intracellular complex formation was not the whole story. "A key additional finding was the 'CellTrap effect' that we discovered," adds biochemist Christian Meyners, also from the Structure-Based Drug Research Group. "This is a general principle by which active substances accumulate in large quantities within cells." This cellular accumulation enhances the efficacy of the newly discovered compounds and allows the active substance to be directed specifically into diseased cells.
"Prostate cancer cells exhibit higher levels of human FK506-binding protein 12 compared to normal prostate epithelial cells; we exploited this fact to direct a cytotoxic drug specifically to the cancer cells," explains cell biologist Ahmed Bulldan from the Research Group on Systems Biology of the Stress Response at TU Darmstadt. When both cell types were treated simultaneously, only the cancer cells died, while the healthy cells remained unharmed. These experiments demonstrate that the CellTrap effect represents a promising addition to the toolkit researchers can use to direct active substances precisely where they are needed.
Ahmed Bulldan et al, Cell type–selective targeting by heterobifunctional protein binders via in-cell enrichment, Nature Communications (2026). DOI: 10.1038/s41467-026-77460-w Journal information: Nature Communications Provided by Technische Universitat Darmstadt Swati Mestri holds a bachelor's degree in Electronics Engineering and has worked as a content editor since 2019. She has experience editing research documents across technology, health care, and materials science, and has a particular interest in technology and space.
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