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There are currently no clinically effective drugs for the treatment of AKI, excluding adjuvant therapy. In this study, a porous silicon\u2010based nanocarrier rich in disulfide bond skeleton (&lt;50\u00a0nm) is developed that enables efficient co\u2010loading of the hydrophilic drug borane amino complex and the hydrophobic drug BAPTA\u2010AM, with its outer layer sealed by the renal tubule\u2010targeting peptide PEG\u2010LTH. Once targeted to the kidney injured site, the nanocarrier structure collapses in the high glutathione environment of the early stage of AKI, releasing the drugs. Under the action of the slightly acidic inflammatory environment and intracellular esterase, the released drugs produce hydrogen and BAPTA, which can rapidly eliminate the excess ROS and overloaded Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , blocking endoplasmic reticulum\/mitochondrial apoptosis pathway (ATF4\u2010CHOP\u2010Bax axis, Casp\u201012\u2010Casp\u20103 axis, Cyt\u2010C\u2010Casp\u20103 axis) and inflammatory pathway (TNF\u2010\u03b1\u2010NF\u2010\u03baB axis) from the source, thus rescuing the renal cells in the \u201ccritical survival\u201d state and further restoring the kidney function. Overall, this nanoparticle shows substantial clinical promise as a potential therapeutic strategy for I\/R injury\u2010related diseases.\n                  <\/jats:p>","DOI":"10.1002\/smll.202206936","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T14:42:24Z","timestamp":1675176144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Rapidly Blocking the Calcium Overload\/ROS Production Feedback Loop to Alleviate Acute Kidney Injury via Microenvironment\u2010Responsive BAPTA\u2010AM\/BAC Co\u2010Delivery Nanosystem"],"prefix":"10.1002","volume":"19","author":[{"given":"Jiahui","family":"Yan","sequence":"first","affiliation":[{"name":"Frontiers Science Center for Deep Ocean Multispheres and Earth Systems and Key Laboratory of Marine Chemistry Theory and Technology Ministry of Education Ocean University of China  Qingdao 266100 P. R. 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