Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes.
Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes.
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心脏病是世界范围内死亡的主要原因。需要开发一种药物递送系统，其可以特异性地靶向受伤的心脏并递送治疗剂。纳米粒子是一种有前途的选择，靶向药物输送在临床前和临床研究。然而，目前基于纳米颗粒的药物递送系统在靶向心脏组织方面没有足够的特异性。在这项研究中，我们设计了心脏靶向肽，专注于心肌细胞膜中存在的分子。来自细胞和动物研究的数据表明，当纳米颗粒与这些肽缀合时，它们与心肌细胞的结合亲和力显着提高。因此，我们正在开发一种靶向系统，可用于将治疗性化合物特异性地递送至心肌细胞以治疗心脏病。背景资料：纳米颗粒（NPs）已被广泛用作药物递送系统来控制治疗剂的释放以治疗心脏损伤。然而，尽管利用基于NP的药物递送用于治疗心脏疾病的优点，但目前的递送系统在靶向心脏组织方面缺乏特异性，因此限制了其应用。方法：我们创建了三个线性肽，每个由16-24个氨基酸组成。这些肽缀合在NP的表面上，导致形成心脏靶向肽（CTP）-NP（命名为CTP-NP 1、CTP-NP 2和CTP-NP 3）。为了评估它们的有效性，我们比较了这三种CTP-NP与人和小鼠心肌细胞的结合效率。此外，我们在将CTP-NP静脉内注射到成年C57 BL/6 J小鼠中后24小时测定了它们的分布。结果如下：当与不含CTP的对照NP（Con-NP）相比时，所有三种CTP-NP在体外均表现出对人和小鼠心肌细胞的显著增加的结合亲和力，并且在体内在小鼠心脏中的保留增强。对心脏切片的全面评估表明，CTP-NP 3对体内心肌细胞的结合特异性显著大于Con-NP。三种CTP-NP均未被证明引起心肌细胞凋亡。结论：CTP-NP 3具有生物相容性和安全性，可通过与心肌细胞结合靶向心脏。这种靶向特定分子包被的纳米颗粒的方法可能有助于将治疗化合物递送到心肌细胞，用于治疗心脏病，对其他组织具有高疗效和低毒性。
Heart disease is the leading cause of death worldwide. There is a need to develop a drug delivery system that can specifically target injured hearts and deliver therapeutic agents. Nanoparticles are a promising option for targeted drug delivery in both preclinical and clinical studies. However, the current nanoparticle-based drug delivery system does not have enough specificity in targeting the cardiac tissue. In this study, we have designed cardiac targeting peptides that focus on the molecules present in the cardiomyocyte membrane. Data from cell and animal studies have shown that when nanoparticles are conjugated with these peptides, their binding affinity to cardiomyocytes significantly improves. Therefore, we are developing a targeting system that can be utilized to deliver therapeutic compounds specifically to cardiomyocytes for the treatment of heart diseases. Background: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. Methods: We created three linear peptides, each consisting of 16–24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. Results: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. Conclusions: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues.
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DOI：
10.1615/critrevtherdrugcarriersyst.v26.i6.10
发表时间：
2009
影响因子：
2.7
作者：
Puri A;Loomis K;Smith B;Lee JH;Yavlovich A;Heldman E;Blumenthal R
通讯作者：
Blumenthal R
影响因子：
3.5
作者：
Ikuta, T;Sogawa, N;Matsumoto, K
通讯作者：
Matsumoto, K
影响因子：
8
作者：
Bozzuto G;Molinari A
通讯作者：
Molinari A
DOI：
10.1038/s41573-020-0090-8
发表时间：
2021-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Mitchell MJ;Billingsley MM;Haley RM;Wechsler ME;Peppas NA;Langer R
通讯作者：
Langer R
影响因子：
37.8
作者：
Page, Robert L., II;O'Bryant, Cindy L.;Lindenfeld, JoAnn
通讯作者：
Lindenfeld, JoAnn