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Invasive interventional procedures and medications are applied to attenuate the attacks associated with ischemic heart disease by reestablishing blood flow and restoring oxygen supply. However, the overactivation of inflammatory responses and unsatisfactory drug delivery efficiency in the infarcted regions prohibit functional improvement. Here, a nanoengineered monocyte (MO)\u2010based biohybrid system, referred to as CTAs @MOs, for the heart\u2010targeted delivery of combinational therapeutic agents (CTAs) containing anti\u2010inflammatory IL\u201010 and cardiomyogenic miR\u201019a to overcome the limitation of malperfusion within the infarcted myocardium through a polyphenol\u2010mediated interfacial assembly, is reported. Systemic administration of CTAs@MOs bypasses extensive thoracotomy and intramyocardial administration risks, leading to infarcted heart\u2010specific accumulation and sustained release of therapeutic agents, enabling immunomodulation of the proinflammatory microenvironment and promoting cardiomyocyte proliferation in sequence. Moreover, CTAs@MOs, which serve as a cellular biohybrid\u2010based therapy, significantly improve cardiac function as evidenced by enhanced ejection fractions, increased fractional shortening, and diminished infarct sizes. This polyphenol nanoengineered biohybrid system represents a general and potent platform for the efficient treatment of cardiovascular disorders.<\/jats:p>","DOI":"10.1002\/adhm.202403595","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T06:55:15Z","timestamp":1731308115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polyphenol\u2010Nanoengineered Monocyte Biohybrids for Targeted Cardiac Repair and Immunomodulation"],"prefix":"10.1002","volume":"14","author":[{"given":"Jiawen","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guidong","family":"Gong","sequence":"additional","affiliation":[{"name":"BMI Center for Biomass Materials and Nanointerfaces National Engineering Laboratory for Clean Technology of Leather Manufacture Ministry of Education Key Laboratory of Leather Chemistry and Engineering College of Biomass Science and Engineering Sichuan University  Chengdu Sichuan 610065 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiang","family":"He","sequence":"additional","affiliation":[{"name":"BMI Center for Biomass Materials and Nanointerfaces National Engineering Laboratory for Clean Technology of Leather Manufacture Ministry of Education Key Laboratory of Leather Chemistry and Engineering College of Biomass Science and Engineering Sichuan University  Chengdu Sichuan 610065 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"BMI Center for Biomass Materials and Nanointerfaces National Engineering Laboratory for Clean Technology of Leather Manufacture Ministry of Education Key Laboratory of Leather Chemistry and Engineering College of Biomass Science and Engineering Sichuan University  Chengdu Sichuan 610065 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglian","family":"He","sequence":"additional","affiliation":[{"name":"BMI Center for Biomass Materials and Nanointerfaces National Engineering Laboratory for Clean Technology of Leather Manufacture Ministry of Education Key Laboratory of Leather Chemistry and Engineering College of Biomass Science and Engineering Sichuan University  Chengdu Sichuan 610065 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of Pediatric Dentistry West China Second University Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongmin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy University of Illinois at Chicago  Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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