Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury
Abstract Small interfering RNA (siRNA) therapies hold great potential for treating myocardial ischemia-reperfusion injury (MIRI); while their practical application is limited by the low bioavailability, off-target effects, and poor therapeutic efficacy. Here, we present an innovative engineered neut...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03172-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850190993604739072 |
|---|---|
| author | Yaohui Jiang Rongyan Jiang Zequn Xia Meng Guo Yanan Fu Xiaocheng Wang Jun Xie |
| author_facet | Yaohui Jiang Rongyan Jiang Zequn Xia Meng Guo Yanan Fu Xiaocheng Wang Jun Xie |
| author_sort | Yaohui Jiang |
| collection | DOAJ |
| description | Abstract Small interfering RNA (siRNA) therapies hold great potential for treating myocardial ischemia-reperfusion injury (MIRI); while their practical application is limited by the low bioavailability, off-target effects, and poor therapeutic efficacy. Here, we present an innovative engineered neutrophil membrane-camouflaged nanocomplex for targeted siRNA delivery and effective MIRI therapy. A nanoparticle (NP)-based siRNA delivery system, namely MNM/siRNA NPs, is camouflaged with neutrophil membranes modified by hemagglutinin (HA) and integrins. Our comprehensive in vitro studies show that MNM/siRNA NPs effectively facilitate endosomal escape through HA, achieve excellent targeting via integrins, and significantly reduce integrin α9 expression. Furthermore, in MIRI mice, we identify integrin α9 as a potential target for MIRI therapy and demonstrate that MNM/siRNA NPs significantly decrease myocardial infarction area and improve cardiac function by reducing neutrophil recruitment, neutrophil extracellular trap (NET) and microthrombus formation. These findings highlight the engineered membrane-camouflaged NPs as a promising siRNA delivery platform, offering an effective treatment strategy for MIRI. |
| format | Article |
| id | doaj-art-e2e5d255a09c4167bdfc87b4c50770f0 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-e2e5d255a09c4167bdfc87b4c50770f02025-08-20T02:15:02ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111910.1186/s12951-025-03172-wEngineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injuryYaohui Jiang0Rongyan Jiang1Zequn Xia2Meng Guo3Yanan Fu4Xiaocheng Wang5Jun Xie6Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Cardiology, Affiliated Bozhou Hospital of Anhui Medical UniversityDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Cardiology, National Cardiovascular Disease Regional Center for Anhui, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract Small interfering RNA (siRNA) therapies hold great potential for treating myocardial ischemia-reperfusion injury (MIRI); while their practical application is limited by the low bioavailability, off-target effects, and poor therapeutic efficacy. Here, we present an innovative engineered neutrophil membrane-camouflaged nanocomplex for targeted siRNA delivery and effective MIRI therapy. A nanoparticle (NP)-based siRNA delivery system, namely MNM/siRNA NPs, is camouflaged with neutrophil membranes modified by hemagglutinin (HA) and integrins. Our comprehensive in vitro studies show that MNM/siRNA NPs effectively facilitate endosomal escape through HA, achieve excellent targeting via integrins, and significantly reduce integrin α9 expression. Furthermore, in MIRI mice, we identify integrin α9 as a potential target for MIRI therapy and demonstrate that MNM/siRNA NPs significantly decrease myocardial infarction area and improve cardiac function by reducing neutrophil recruitment, neutrophil extracellular trap (NET) and microthrombus formation. These findings highlight the engineered membrane-camouflaged NPs as a promising siRNA delivery platform, offering an effective treatment strategy for MIRI.https://doi.org/10.1186/s12951-025-03172-wEngineered neutrophil membraneMyocardial ischemia-reperfusion injuryNeutrophilsIntegrin α9siRNA |
| spellingShingle | Yaohui Jiang Rongyan Jiang Zequn Xia Meng Guo Yanan Fu Xiaocheng Wang Jun Xie Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury Journal of Nanobiotechnology Engineered neutrophil membrane Myocardial ischemia-reperfusion injury Neutrophils Integrin α9 siRNA |
| title | Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury |
| title_full | Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury |
| title_fullStr | Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury |
| title_full_unstemmed | Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury |
| title_short | Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury |
| title_sort | engineered neutrophil membrane camouflaged nanocomplexes for targeted sirna delivery against myocardial ischemia reperfusion injury |
| topic | Engineered neutrophil membrane Myocardial ischemia-reperfusion injury Neutrophils Integrin α9 siRNA |
| url | https://doi.org/10.1186/s12951-025-03172-w |
| work_keys_str_mv | AT yaohuijiang engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury AT rongyanjiang engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury AT zequnxia engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury AT mengguo engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury AT yananfu engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury AT xiaochengwang engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury AT junxie engineeredneutrophilmembranecamouflagednanocomplexesfortargetedsirnadeliveryagainstmyocardialischemiareperfusioninjury |