{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:56:02Z","timestamp":1780667762434,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program of the National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2022R1A4A2000767"],"award-info":[{"award-number":["2022R1A4A2000767"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program of the National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["GTL24000-000"],"award-info":[{"award-number":["GTL24000-000"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program of the National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["RS-2024-00466906"],"award-info":[{"award-number":["RS-2024-00466906"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Council of Science and Technology(NST)","award":["2022R1A4A2000767"],"award-info":[{"award-number":["2022R1A4A2000767"]}]},{"name":"National Research Council of Science and Technology(NST)","award":["GTL24000-000"],"award-info":[{"award-number":["GTL24000-000"]}]},{"name":"National Research Council of Science and Technology(NST)","award":["RS-2024-00466906"],"award-info":[{"award-number":["RS-2024-00466906"]}]},{"name":"Korea\u2013US Collaborative Research Fund","award":["2022R1A4A2000767"],"award-info":[{"award-number":["2022R1A4A2000767"]}]},{"name":"Korea\u2013US Collaborative Research Fund","award":["GTL24000-000"],"award-info":[{"award-number":["GTL24000-000"]}]},{"name":"Korea\u2013US Collaborative Research Fund","award":["RS-2024-00466906"],"award-info":[{"award-number":["RS-2024-00466906"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heart failure (HF) remains a major cause of mortality worldwide. While novel approaches, including gene and cell therapies, show promise, efficient delivery methods for such biologics to the heart are critically needed. One emerging strategy is lung-to-heart delivery using nanoparticle (NP)-encapsulated biologics. This study examines the efficiency of delivering a therapeutic peptide conjugated to a cell-penetrating peptide (CPP) to the heart via the lung-to-heart route through intratracheal (IT) injection in mice. The CPP, a tandem repeat of NP2 (dNP2) derived from the human novel LZAP-binding protein (NLBP), facilitates intracellular delivery of the therapeutic payload. The therapeutic peptide, SE, is a decoy peptide designed to inhibit protein phosphatase 1 (PP1)-mediated dephosphorylation of phospholamban (PLN). Our results demonstrated that IT injection of dNP2-SE facilitated efficient delivery to the heart, with peak accumulation at 3 h post-injection. The administration of dNP2-SE significantly ameliorated morphological and functional deterioration of the heart under myocardial infarction. At the molecular level, dNP2-SE effectively prevented PLN dephosphorylation in the heart. Immunoprecipitation experiments further revealed that dNP2-SE binds strongly to PP1 and disrupts its interaction with PLN. Collectively, our findings suggest that lung-to-heart delivery of a CPP-conjugated therapeutic peptide, dNP2-SE, represents a promising approach for the treatment of HF.<\/jats:p>","DOI":"10.3390\/ijms26062649","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:07:51Z","timestamp":1741957671000},"page":"2649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intratracheal Delivery of a Phospholamban Decoy Peptide Attenuates Cardiac Damage Following Myocardial Infarction"],"prefix":"10.3390","volume":"26","author":[{"given":"Taewon","family":"Kook","sequence":"first","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"BethphaGen, S3-203, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hwan","family":"Kwak","sequence":"additional","affiliation":[{"name":"BethphaGen, S3-203, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-3498","authenticated-orcid":false,"given":"Dongtak","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medicinal & Life Science, College of Science and Convergence Technology, Hanyang University-ERICA, Ansan 15588, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4162-7902","authenticated-orcid":false,"given":"Doo Sun","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Ho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2022-9366","authenticated-orcid":false,"given":"Youngkeun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Chonnam National University Hospital, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-1806","authenticated-orcid":false,"given":"Hyun","family":"Kook","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chonnam National University Medical School, Hwasun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jin","family":"Park","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"},{"name":"BethphaGen, S3-203, Gwangju 61005, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Pil","family":"Jang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea"},{"name":"Center for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ehf2.14857","article-title":"2024 update in heart failure","volume":"12","author":"Beghini","year":"2024","journal-title":"ESC Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1093\/cvr\/cvac013","article-title":"Global burden of heart failure: A comprehensive and updated review of epidemiology","volume":"118","author":"Savarese","year":"2023","journal-title":"Cardiovasc. 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