{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:21:08Z","timestamp":1783066868216,"version":"3.54.6"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/n\/a","name":"The Second Affiliated Hospital of Chongqing Medical University","doi-asserted-by":"publisher","award":["rsc-postdoctor235"],"award-info":[{"award-number":["rsc-postdoctor235"]}],"id":[{"id":"10.13039\/n\/a","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heart transplantation is an optimal therapeutic regimen for terminal-stage cardiac failure. However, cold ischemia-reperfusion injury (CIRI) remains an unavoidable and outstanding challenge, which is a significant obstacle to early graft dysfunction and long-term survival. Blockage of complement, apoptosis, and inflammation by small interfering RNA is considered a strategy for attenuating CIRI and protecting cardiac function. However, their delivery to the donor organ is still a serious challenge due to the polyanionic nature and high molecular weight properties. Here, we have designed a novel functionalized gene delivery system of direct delivery and sustained release of siRNAs targeting complement C3 (C3), Caspase-3, and nuclear factor \u03baB (NF-\u03baB) to treat the donor organ prior to transplantation. The functionalized gene delivery system (siRNA-TNPs), composed of CaCO3\/CaP\/TAT embellished carboxymethyl chitosan (CaCO3\/CaP\/TCMC) and synthesized through the co-precipitation method, efficiently encapsulates siRNAs during self-assembly. The siRNA-TNPs safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and enhances the delivery efficiency of siRNA to the donor hearts. Perfusion of donor hearts with siRNA-TNPs prior to transplantation attenuated C3, Caspase-3, and NF-\u03baB genes expression of donor heart for at least 5\u00a0days after transplantation. Furthermore, silencing of C3, Caspase-3, and NF-\u03baB genes expression alleviated cell apoptosis, myocardial damage, tissue inflammation, and rejection and improved cardiac function. These data suggest that the multiple-target siRNA-TNPs solution can extend the preservation time for donor grafts, attenuate IRI, and protect cardiac function in murine models of heart transplantation, which provides a principal of concept for potential clinical translation.<\/jats:p>","DOI":"10.1042\/cs20250653","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:08:09Z","timestamp":1782299289000},"page":"1551-1573","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Ex vivo<\/i>\n                    pretreatment of donor organ with siRNA nanoparticles attenuates cold ischemia-reperfusion injury in cardiac transplantation"],"prefix":"10.1042","volume":"140","author":[{"given":"Shun","family":"Yuan","sequence":"first","affiliation":[{"name":"1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"},{"name":"2Central Laboratory, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Che","sequence":"additional","affiliation":[{"name":"1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"},{"name":"2Central Laboratory, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Bo","sequence":"additional","affiliation":[{"name":"1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyang","family":"Chen","sequence":"additional","affiliation":[{"name":"3Department of Cardiovascular Surgery, Wuhan University Renmin Hospital, 238# Jiefang Road, Wuhan 430000, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Xie","sequence":"additional","affiliation":[{"name":"3Department of Cardiovascular Surgery, Wuhan University Renmin Hospital, 238# Jiefang Road, Wuhan 430000, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Du","sequence":"additional","affiliation":[{"name":"1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7977-5258","authenticated-orcid":false,"given":"Lin","family":"Shen","sequence":"additional","affiliation":[{"name":"1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Chongqing Medical University, 288# Tianwen Avenue, Chongqing City, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"2026070304014969600_B1","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.healun.2022.10.015","article-title":"The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients","volume":"42","author":"Velleca","year":"2023","journal-title":"J. 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