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Herein, we report\n                    <jats:styled-content>Cl<\/jats:styled-content>\n                    ick\u2010activated\n                    <jats:styled-content>Sup<\/jats:styled-content>\n                    ramolecular\n                    <jats:styled-content>TA<\/jats:styled-content>\n                    rgeting\n                    <jats:styled-content>C<\/jats:styled-content>\n                    himeras (\n                    <jats:bold>ClSupTAC<\/jats:bold>\n                    ), a multimodular platform leveraging bioorthogonal chemistry to realize spatially and temporally resolved TPD in vivo.\n                    <jats:bold>ClSupTAC<\/jats:bold>\n                    follows a two\u2010step \u201cclick\u2010to\u2010activate\u201d paradigm: self\u2010assembled, functionally dormant tissue\u2010targeting supramolecular nanoparticles presenting protein\u2010binding ligands and\n                    <jats:italic>trans<\/jats:italic>\n                    \u2010cyclooctene (TCO) moieties are locally activated upon inverse electron\u2010demand Diels\u2013Alder (IEDDA) cycloaddition with tetrazine\u2010E3 ubiquitin ligase recruiter conjugates. The IEDDA chemistry of\n                    <jats:bold>ClSupTAC<\/jats:bold>\n                    delivers accelerated addition reaction and protein degradation kinetics compared to Staudinger reaction\u2010mediated activation of TPD. Moreover,\n                    <jats:bold>ClSupTAC<\/jats:bold>\n                    achieves rapid, selective degradation of pathogenic proteins in vitro and enables lung\u2010targeted protein degradation in vivo. In acute lung injury models,\n                    <jats:bold>ClSupTAC<\/jats:bold>\n                    effectively alleviates pulmonary inflammation and recovers vascular barrier integrity. This study establishes\n                    <jats:bold>ClSupTAC<\/jats:bold>\n                    as a versatile and programmable platform for spatiotemporally precise protein regulation and targeted therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1002\/anie.2233329","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:23:47Z","timestamp":1788927827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Click\u2010Activated Supramolecular Targeting Chimeras for Spatiotemporally Resolved Protein Degradation In Vivo"],"prefix":"10.1002","author":[{"given":"Yongsong","family":"Zhang","sequence":"first","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences CAS Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing 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