In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles
In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles
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DOI：
10.1016/j.jconrel.2006.01.006
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发表时间：
2006-05-01
影响因子：
10.8
通讯作者：
Swartz, MA
中科院分区：
文献类型：
--
作者：
Reddy, ST;Rehor, A;Swartz, MA
将可生物降解的纳米颗粒递送到抗原呈递细胞（APCs），特别是树突状细胞（DCs），具有免疫治疗的潜力。本研究研究了20、45和100nm直径的聚（乙二醇）稳定聚（丙烯硫化物）（PPS）纳米颗粒对淋巴结DCs的递送。这些纳米颗粒由交联的PPS橡胶核心组成，周围是聚乙二醇的亲水性电晕。PPS结构域能够携带疏水药物并在氧化环境中降解。20 nm的纳米颗粒在注射后最容易进入淋巴组织，而20和45nm的纳米颗粒在淋巴结中都表现出明显的滞留，在注射后24、72、96和120小时表现出一致和强烈的存在。在不使用靶向配体的情况下，高达40-50%的淋巴结dc（和apc）内化了纳米颗粒，并且内化部位在淋巴结而不是注射部位。最后，96小时与24小时相比，含有纳米颗粒的DCs（和其他apc）增加，表明这些细胞浸润到淋巴结。因此，20-45nm的PPS纳米颗粒具有特异性靶向淋巴结dc的免疫治疗应用潜力。(c) 2006 Elsevier B.V.版权所有
Delivery of biodegradable nanoparticles to antigen-presenting cells (APCs), specifically dendritic cells (DCs), has potential for immunotherapy. This study investigates the delivery of 20, 45, and 100nm diameter poly(ethylene glycol)-stabilized poly(propylene sulfide) (PPS) nanoparticles to DCs in the lymph nodes. These nanoparticles consist of a cross-linked rubbery core of PPS surrounded by a hydrophilic corona of poly(ethylene glycol). The PPS domain is capable of carrying hydrophobic drugs and degrades within oxidative environments. 20 nm particles were most readily taken up into lymphatics following interstitial injection, while both 20 and 45nm nanoparticles showed significant retention in lymph nodes, displaying a consistent and strong presence at 24, 72, 96 and 120h post-injection. Nanoparticles were internalized by up to 40-50% of lymph node DCs (and APCs) without the use of a targeting ligand, and the site of internalization was in the lymph nodes rather than at the injection site. Finally, an increase in nanoparticle-containing DCs (and other APCs) was seen at 96h vs. 24h, suggesting an infiltration of these cells to lymph nodes. Thus, PPS nanoparticles of 20-45nm have the potential for immunotherapeutic applications that specifically target DCs in lymph nodes. (c) 2006 Elsevier B.V. All rights reserved.