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Here, incorporating MnOx into the porphyrinic Zr-MOF PCN-224 modulates the coordination environment of Zr6 clusters, suppressing phosphate-induced linker displacement and extending structural integrity under physiological conditions. The optimized 1:1 MnOx@PCN-224 formulation resists phosphate-triggered disassembly and porphyrin release in phosphate-buffered saline (PBS). MnOx also acts as a catalase mimic, converting endogenous H2O2 into O2 to relieve tumor hypoxia and potentiate sonodynamic therapy (SDT). Under high-intensity focused ultrasound (HIFU) irradiation, stabilized porphyrin linkers generate enhanced 1O2 levels. Functionalization with GST-EGFR as a preadsorbed targeting protein corona enables tumor-specific delivery, and the resulting nanoplatform suppresses tumor growth in a 4T1 breast tumor model. This coordination-driven strategy transforms the inherent lability of Zr-MOFs into a designable parameter for engineering biointerface stability for in vivo therapeutic applications.<\/jats:p>","DOI":"10.1021\/acs.biomac.6c00899","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:01:51Z","timestamp":1786359711000},"page":"6033-6043","source":"Crossref","is-referenced-by-count":1,"title":["Coordination-Driven\nProgramming of MOF Stability via\nTargeting Protein Corona Engineering for Hypoxia-Relieving Sonodynamic\nTherapy"],"prefix":"10.1021","volume":"27","author":[{"given":"Youjung","family":"Sim","sequence":"first","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeongseok","family":"Yang","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]},{"name":"Gwangju Institute of Science and Technology , , ,","place":["Gwangju, Republic of Korea, 61005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5123-418X","authenticated-orcid":true,"given":"Joohan","family":"Nam","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungo","family":"Baek","sequence":"additional","affiliation":[{"name":"Nanyang Technological University (NTU) , , 50 Nanyang Avenue , ,","place":["Singapore, Singapore, 639798"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-9794","authenticated-orcid":true,"given":"Jung Heum","family":"Yoon","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Pohang Accelerator Laboratory\/POSTECH , , , ,","place":["Pohang, Gyeongbuk, Republic of Korea, 37673"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-5232","authenticated-orcid":true,"given":"Eunshil","family":"Choi","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-5808","authenticated-orcid":true,"given":"Gun","family":"Kim","sequence":"additional","affiliation":[{"name":"Nanyang Technological University (NTU) , , 50 Nanyang Avenue , ,","place":["Singapore, Singapore, 639798"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-1187","authenticated-orcid":true,"given":"Wonyoung","family":"Choe","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]},{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]},{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]},{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0252-0985","authenticated-orcid":true,"given":"Ja-Hyoung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Ulsan National Institute of Science and Technology (UNIST) , , ,","place":["Ulsan, Republic of Korea, 44919"]},{"name":"Gwangju Institute of Science and Technology , , ,","place":["Gwangju, Republic of Korea, 61005"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"26","key":"2026091407070673100_cit1","doi-asserted-by":"publisher","first-page":"2312169","DOI":"10.1002\/adma.202312169","article-title":"Nanomedicine\nTumor Targeting","volume":"36","author":"Lammers","year":"2024","journal-title":"Adv. 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