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Here we present a near\u2010infrared (NIR) light\u2010controlled nanosystem that allows spatiotemporally controlled regulation of gene expression and thus combinational tumor therapy. The nanosystem is built by engineering of an enzyme\u2010activatable antisense oligonucleotide and further combination with an upconversion nanoparticle\u2010based photodynamic system and a mitochondria localization signal. The system relies on photodynamic effect\u2010induced translocation of a DNA repair enzyme from nucleus into mitochondria, which enables spatially selective gene regulation via enzymatic reactions. We demonstrate that the NIR light\u2010induced mitochondrial photodamage and gene regulation enable enhanced antitumor effect. Our approach may enable the specific gene regulation and tumor treatment with high precision both spatially and temporally.<\/jats:p>","DOI":"10.1002\/anie.202217702","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T23:04:42Z","timestamp":1678835082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A Remotely Controlled Nanosystem for Spatiotemporally Specific Gene Regulation and Combinational Tumor Therapy"],"prefix":"10.1002","volume":"62","author":[{"given":"Xin","family":"Chai","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology  Beijing 100190 China"},{"name":"College of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences  Beijing 100049 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