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siRNA Delivery against Myocardial Ischemia Reperfusion Injury Mediated by Reversibly Camouflaged Biomimetic Nanocomplexes.
Zhou, Yang; Liang, Qiujun; Wu, Xuejie; Duan, Shanzhou; Ge, Chenglong; Ye, Huan; Lu, Jianhui; Zhu, Rongying; Chen, Yongbing; Meng, Fenghua; Yin, Lichen.
Afiliación
  • Zhou Y; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
  • Liang Q; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
  • Wu X; Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
  • Duan S; Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
  • Ge C; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
  • Ye H; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
  • Lu J; Department of Vasculocardiology, Haimen Traditional Chinese Medicine Hospital, Haimen, 226100, China.
  • Zhu R; Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
  • Chen Y; Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
  • Meng F; Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.
  • Yin L; Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
Adv Mater ; 35(23): e2210691, 2023 Jun.
Article en En | MEDLINE | ID: mdl-36913720
siRNA-mediated management of myocardial ischemia reperfusion (IR) injury is greatly hampered by the inefficient myocardial enrichment and cardiomyocyte transfection. Herein, nanocomplexes (NCs) reversibly camouflaged with a platelet-macrophage hybrid membrane (HM) are developed to efficiently deliver Sav1 siRNA (siSav1) into cardiomyocytes, suppressing the Hippo pathway and inducing cardiomyocyte regeneration. The biomimetic BSPC@HM NCs consist of a cationic nanocore assembled from a membrane-penetrating helical polypeptide (P-Ben) and siSav1, a charge-reversal intermediate layer of poly(l-lysine)-cis-aconitic acid (PC), and an outer shell of HM. Due to HM-mediated inflammation homing and microthrombus targeting, intravenously injected BSPC@HM NCs can efficiently accumulate in the IR-injured myocardium, where the acidic inflammatory microenvironment triggers charge reversal of PC to shed off both HM and PC layers and allow the penetration of the exposed P-Ben/siSav1 NCs into cardiomyocytes. In rats and pigs, BSPC@HM NCs remarkably downregulates Sav1 in IR-injured myocardium, promotes myocardium regeneration, suppresses myocardial apoptosis, and recovers cardiac functions. This study reports a bioinspired strategy to overcome the multiple systemic barriers against myocardial siRNA delivery, and holds profound potential for gene therapy against cardiac injuries.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión Miocárdica Límite: Animals Idioma: En Revista: Adv Mater Asunto de la revista: BIOFISICA / QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión Miocárdica Límite: Animals Idioma: En Revista: Adv Mater Asunto de la revista: BIOFISICA / QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania