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Nevertheless, HIFU may also induce the upregulation of Heat Shock Protein 90 (HSP\u201090), potentially resulting in resistance to HIFU. Besides, although it is effective against in situ tumors, challenges remain with tumor metastasis and recurrence. Herein, the innovative design of gambogic acid (GA) based coordination polymer\u2014GAZn\u2010PEG nanoparticles (GAZn\u2010PEG NPs) are synthesized through the coordination of GA with zinc ions (Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ), and subsequently functionalized with lipid bilayer incorporating polyethylene glycol (PEG), sensitizing HIFU for the treatment of cervical and ovarian cancers. Briefly, under HIFU exposure, GA markedly suppresses the expression of HSP\u201090, thereby increasing the tumor's sensitivity to HIFU therapy. Furthermore, Zn\n                    <jats:sup>2+<\/jats:sup>\n                    not only overcome the issue of GA's poor water solubility but also synergistically stimulate immune responses in conjunction with GA. More intriguingly, it has been discovered that GAZn\u2010PEG can effectively activate the cyclic GMP\u2010AMP synthase\u2010stimulator of the interferon genes (cGAS\u2010STING) pathway, thereby enhancing the immune responses provoked by HIFU. Specifically, GAZn\u2010PEG NPs show a remarkable increase in dendritic cell activation and the effective stimulation of the cGAS\u2010STING pathway, crucial for long\u2010term protection against tumor recurrence and metastasis.\n                  <\/jats:p>","DOI":"10.1002\/adma.202501664","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T03:00:40Z","timestamp":1744599640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gambogic Acid Based Coordination Polymer Reinforces High\u2010Intensity Focused Ultrasound Treatment of Gynecologic Malignancies"],"prefix":"10.1002","volume":"37","author":[{"given":"Lin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Municipal Key Clinical 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&amp; Devices Soochow University  Suzhou 215123 China"},{"name":"Department of Gynecology The Fourth Affiliated Hospital of Soochow University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200030 China"},{"name":"Shanghai Municipal Key Clinical Specialty Female Tumor Reproductive Specialty  Shanghai 200030 China"},{"name":"National Center for Translational Medicine (Shanghai) \u2014 Maternal and Children's Branch  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 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