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Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single\u2010protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye\u2010peptide conjugate, PRFK, for multi\u2010protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein\u00a0located in the endoplasmic reticulum (ER). The dye generates <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub> under light irradiation, enabling photodynamic therapy. This process\u00a0converts the furan group into a cytidine\u2010reactive intermediate, which\u00a0covalently\u00a0binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi\u2010protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi\u2010protein interference probe with the potential for protein interference within various subcellular organelles in the future.<\/jats:p>","DOI":"10.1002\/adhm.202304108","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T07:44:19Z","timestamp":1720511059000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatiotemporally Controllable Covalent Bonding of RNA for Multi\u2010Protein Interference"],"prefix":"10.1002","volume":"13","author":[{"given":"Hao","family":"Fang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biogeology and Environmental Geology Faculty of Materials Science and Chemistry China University of Geosciences  Wuhan 430074 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biogeology and Environmental 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