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For example, the photosensitizers tend to clump together, which causes fluorescence to drop sharply. They also do not produce enough singlet oxygen, and they cannot accurately reach the specific parts of cancer cells that need to be targeted. To address these bottlenecks, we designed and fabricated a new amphiphilic metallacycle based on pillar[5]arene and Pt(II), which we named AmMeCy. This material has a special two-cavity structure that has never been reported before. One cavity comes from the pillar[5]arene part and can precisely hold targeting molecules through host-guest interaction, The other cavity is formed by the Pt-coordinated metallacycle, which helps to confine the structure and control its functions. Notably, Pt coordination effectively restricts the \u03c0-\u03c0 stacking of porphyrin moieties, fundamentally eliminating aggregation-caused quenching (ACQ) and significantly boosting fluorescence emission and 1O2 photogeneration efficiency. Benefiting from its amphiphilic nature, the metallacycle can spontaneously self-assemble into uniform nanostructures in aqueous media with excellent water dispersibility and biocompatibility. After host-guest encapsulation of mitochondrial-targeted guests, the assembled nanoparticles (AmMeCy \u2283 TPP NPs) achieve precise mitochondrial localization in tumor cells. Upon light irradiation, the amplified 1O2 burst efficiently triggers mitochondrial oxidative damage and tumor cell apoptosis. This work establishes a new dual-cavity supramolecular platform via metal-ligand coordination and pillararene host-guest chemistry, providing a facile and universal strategy for the structural optimization and functional upgrading of high-efficiency tumor PDT nanotherapeutics.<\/jats:p>","DOI":"10.1021\/acs.inorgchem.6c03336","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:01:39Z","timestamp":1788778899000},"page":"21920-21929","source":"Crossref","is-referenced-by-count":0,"title":["Amphiphilic\nPillar[5]arene-Based Pt(II)-Coordinated\nDual-Cavity Metallacycle: Construction and Application in Enhanced\nMitochondrial Photodynamic Cancer Therapy"],"prefix":"10.1021","volume":"65","author":[{"given":"Fengqin","family":"Wang","sequence":"first","affiliation":[{"name":"Nantong Institute of Technology , , ,","place":["Nantong, Jiangsu, China, 226006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Wang","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Duan","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Yuan","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Deng","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Chen","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cai","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2500-5708","authenticated-orcid":true,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5566-4822","authenticated-orcid":true,"given":"Yong","family":"Yao","sequence":"additional","affiliation":[{"name":"Nantong Institute of Technology , , ,","place":["Nantong, Jiangsu, China, 226006"]},{"name":"Nantong University , , , ,","place":["Nantong, Jiangsu, China, 226019"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026092108521805900_cit1","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1021\/acsnano.5c18698","article-title":"Supramolecular Metallacycle\nEnables Esterase-Responsive and Endoplasmic\nReticulum-Associated Pathway Activation for Synergistic Photothermal\nImmunotherapy","volume":"20","author":"Chen","year":"2026","journal-title":"ACS Nano"},{"key":"2026092108521805900_cit2","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1021\/jacs.5c15389","article-title":"Ultrasound-Triggered\nType I Supramolecular\nPhotosensitizer for Precise In Situ Chemiluminescence-Based Photodynamic\nCyclic Therapy","volume":"148","author":"Li","year":"2026","journal-title":"J. Am. Chem. Soc."},{"key":"2026092108521805900_cit3","doi-asserted-by":"publisher","first-page":"5026","DOI":"10.1039\/D4QI01288G","article-title":"Synthesis\nand near-infrared photothermal conversion of Cp*Rh-based [2]-catenanes\nin trapezoidal metallacycles","volume":"11","author":"Hua","year":"2024","journal-title":"Inorg. Chem. Front."},{"key":"2026092108521805900_cit4","doi-asserted-by":"publisher","first-page":"30222","DOI":"10.1021\/jacs.4c09282","article-title":"Pyrene-Functionalized\nRu-Catenated Metallacycles: Conversion of Catenated System to Monorectangle\nthrough Aging","volume":"146","author":"Gupta","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"2026092108521805900_cit5","doi-asserted-by":"publisher","first-page":"21948","DOI":"10.1021\/acs.inorgchem.5c03482","article-title":"Cu@Core\nin the Cu3C3 Ring with 2-bdppmapy: A High-Quantum-Yield\nPlanar Hexagonal\nCu(I) Metallacycle","volume":"64","author":"Fan","year":"2025","journal-title":"Inorg. 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Mater."},{"key":"2026092108521805900_cit44","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1039\/D1QM01630J","article-title":"Amphiphilic\nrhomboidal metallacycles with aggregation-induced emission and aggregation-caused\nquenching luminogens for white-light emission and bioimaging","volume":"6","author":"Fan","year":"2022","journal-title":"Mater. Chem. Front."},{"key":"2026092108521805900_cit45","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1021\/acsmacrolett.9b00914","article-title":"Self-Assembled Saccharide-Functionalized\nAmphiphilic Metallacycles as Biofilms Inhibitor via \u2033Sweet\nTalking\u2033","volume":"9","author":"Tao","year":"2020","journal-title":"ACS Macro Lett."},{"key":"2026092108521805900_cit46","doi-asserted-by":"publisher","first-page":"7141","DOI":"10.1021\/acs.inorgchem.9b01036","article-title":"Self-Assembled Amphiphilic\nJanus Double Metallacycle","volume":"58","author":"Wang","year":"2019","journal-title":"Inorg. 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