Chitosan enhances nanoparticle delivery from the reproductive tract to target draining lymphoid organs.
Chitosan enhances nanoparticle delivery from the reproductive tract to target draining lymphoid organs.
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DOI：
10.1016/j.nano.2017.04.012
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Woodrow KA
中科院分区：
文献类型：
--
作者：
Park J;Ramanathan R;Pham L;Woodrow KA
为了引发来自雌性生殖道（FRT）的适应性免疫应答，必须将颗粒抗原转运至引流淋巴结（dLN），因为不存在与在呼吸道或胃肠道中发现的那些等同的局部组织化淋巴样结构。然而，很少有人知道如何安全有效地通过连续的屏障来运输，如穿过上皮细胞并进入迁移细胞和淋巴引流，从而进入dLN。在这里，我们证明，阴道内预处理与壳聚糖显着促进易位的纳米粒子（NP）的多层阴道上皮细胞的目标dLN。此外，发现壳聚糖预处理增强NP与阴道粘膜下层中免疫原性抗原呈递细胞的结合。这些观察结果表明，壳聚糖可能有很大的潜力作为佐剂的局部和全身保护性免疫对病毒感染的FRT。为了在雌性生殖道中诱导强大的免疫力，给予阴道腔的颗粒抗原必须被转运到排出雌性生殖道的淋巴结。然而，穿过多层鳞状上皮到达引流淋巴结是颗粒抗原的一个巨大障碍。这项研究报告的第一个证据，使用壳聚糖，以促进纳米粒子运输到引流淋巴结。观察表明，安全地克服纳米颗粒的物理屏障是可行的，从而增强疫苗的功效以及药物向阴道途径的递送。
To prime adaptive immune responses from the female reproductive tract (FRT), particulate antigens must be transported to draining lymph nodes (dLNs) since there are no local organized lymphoid structures equivalent to those found in the respiratory or gastrointestinal tracts. However, little is known about how to safely and effectively navigate successive barriers to transport such as crossing the epithelium and gaining access to migratory cells and lymphatic drainage that provide entry into dLNs. Here, we demonstrate that intravaginal pre-treatment with chitosan significantly facilitates translocation of nanoparticles (NPs) across the multilayered vaginal epithelium to target dLNs. In addition, chitosan pre-treatment was found to enhance NP associations with immunogenic antigen presenting cells in the vaginal submucosa. These observations indicate that chitosan may have great potential as an adjuvant for both local and systemic protective immunity against viral infections in the FRT. To induce robust immunity in the female reproductive tract, particulate antigens administered to the vaginal lumen must be transported to lymph nodes that drain the female reproductive tract. However, traversing the multilayered squamous epithelium to reach the draining lymph nodes is a formidable obstacle for particulate antigens. This study reports on the first evidence of using chitosan to facilitate nanoparticle trafficking to the draining lymph nodes. Observations indicate that it is feasible to safely overcome the physical barrier to nanoparticles, thereby enhancing efficacy of vaccines as well as drug delivery to the vaginal route.
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