Liposomes to target peripheral neurons and Schwann cells.
Liposomes to target peripheral neurons and Schwann cells.
复制标题
DOI：
10.1371/journal.pone.0078724
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Notterpek L
中科院分区：
文献类型：
--
作者：
Lee S;Ashizawa AT;Kim KS;Falk DJ;Notterpek L
虽然出现了大量针对组织特异性脂质体的文献，但缺乏针对周围神经系统(PNS)细胞的最佳配方。在这项研究中，我们询问是否可以优化一种新的磷脂基脂质体配方，使其优先被微血管内皮细胞、外周神经元和雪旺细胞摄取。在这里，我们报告了一种独特的配方，它由磷脂、聚合物表面活性物质和胆固醇组成，能够增强靶细胞的摄取。使用荧光标记的脂质体，我们跟随颗粒内化和运输，通过一条与葡聚糖不同的路线，并逃离降解的隔间，如溶酶体。在非髓鞘雪旺细胞的培养中，脂质体与脂筏标志霍乱毒素结合，其内化被脂筏破坏或肌动蛋白聚合抑制。相反，药物抑制蛋白介导的内吞作用不会显著影响脂质体的进入。为了评价脂质体在组织中的靶向性，我们采用了背根节髓鞘外植体培养和分离的横隔膜标本，这两种材料都含有外周神经元和髓鞘雪旺细胞。在这些模型中，我们发现与周围肌肉组织相比，脂质体优先摄取到神经元和神经胶质细胞。此外，通过肌肉注射或静脉注射的体内脂质体给药证实，这些颗粒被输送到有髓外周神经。在中枢神经系统内，我们在脉络膜上皮细胞中检测到脂质体，但在有髓白质区域或脑实质中未检测到脂质体。所描述的纳米颗粒代表了一种新型的亲神经递送载体，可将小的治疗性化合物、生物分子或成像试剂靶向外周神经元和雪旺细胞，并在开发外周神经疾病的有效治疗方法方面取得了重大进展。
While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS) are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral neuropathies.
登录
查看更多内容
影响因子：
4.8
作者：
Donaldson, Julie G.;Porat-Shliom, Natalie;Cohen, Lee Ann
通讯作者：
Cohen, Lee Ann
影响因子：
2.6
作者：
Gutiérrez-Puente, Y;Tari, AM;Lopez-Berestein, G
通讯作者：
Lopez-Berestein, G
影响因子：
4.4
作者：
Rejman, Joanna;Conese, Massimo;Hoekstra, Dick
通讯作者：
Hoekstra, Dick
影响因子：
6.1
作者：
Notterpek, L;Ryan, MC;Shooter, EM
通讯作者：
Shooter, EM
影响因子：
3.8
作者：
Stins, MF;Badger, J;Kim, KS
通讯作者：
Kim, KS