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However, the low therapeutic efficiency still hinders its further biological applications. Herein, via a simple and one\u2010pot gas diffusion process, polyethylene glycol (PEG)\u2010modified Mn<jats:sup>2+<\/jats:sup> ions and usnic acid (UA)\u2010incorporated CaCO<jats:sub>3<\/jats:sub> nanomaterials (<jats:sup>PEG<\/jats:sup>CaMnUA) as Ca<jats:sup>2+<\/jats:sup>\/Mn<jats:sup>2+<\/jats:sup> ions reservoirs are prepared for magnetic resonance imaging (MRI)\u2010guided UA\u2010elevated IIT. Among <jats:sup>PEG<\/jats:sup>CaMnUA, UA not only increases cytoplasmic Ca<jats:sup>2+<\/jats:sup> ions to amplify Ca<jats:sup>2+<\/jats:sup> overload caused by CaCO<jats:sub>3<\/jats:sub> decomposition, but also enhances Mn<jats:sup>2+<\/jats:sup> ions\u2010participated Fenton\u2010like biocatalysis by intracellular H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> generation and glutathione consumption. Then increasing the intracellular oxidative stress and decreasing the triphosadenine supply induce apoptosis together, resulting in UA\u2010boosted IIT. The simple and efficient design of the dual ions reservoirs will contribute to improve the antitumor activity of IIT and further development of calcium\u2010based nanomaterials in the future.<\/jats:p>","DOI":"10.1002\/smll.202300370","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T12:05:08Z","timestamp":1680955508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Usnea Acid\u2010Incorporated Ca<sup>2+<\/sup>\/Mn<sup>2+<\/sup> Ions Reservoirs for Elevated Ion\u2010Interference Therapy through Synergetic Biocatalysis and Osmolarity Imbalance"],"prefix":"10.1002","volume":"19","author":[{"given":"Pan","family":"Zheng","sequence":"first","affiliation":[{"name":"Institute of Frontier and Interdisciplinary Science Shandong University  Qingdao 266237 P. R. 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