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In this work, a pH\u2010responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3\u2010(bromomethyl)\u20104\u2010methyl\u20102,5\u2010furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)\u2010loaded zeolitic imidazolate framework (Ap\u2010ZIF) to form Ap\u2010ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap\u2010ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap\u2010ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap\u2010ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor\u2010bearing mice after injections with Ap\u2010ZIF@SLN#TL. Furthermore, mice show normal tissue structure\u00a0of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH\u2010responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.<\/jats:p>","DOI":"10.1002\/adma.202203915","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T18:54:00Z","timestamp":1660935240000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["A pH\u2010Responsive Cluster Metal\u2013Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7258-9489","authenticated-orcid":false,"given":"Ruoyu","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of General Surgery Pancreatic Disease Center Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin Second Road Shanghai 200025 P. R. China"},{"name":"Department of Biomedical Engineering W.J. 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