Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.
Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.
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DOI：
10.1371/journal.pone.0061646
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Swartz MA
中科院分区：
文献类型：
--
作者：
Kourtis IC;Hirosue S;de Titta A;Kontos S;Stegmann T;Hubbell JA;Swartz MA
纳米颗粒已被广泛开发用于治疗和诊断应用。虽然体内纳米颗粒运输的重点传统上是药物递送和器官水平的生物分布和清除，但最近在癌症生物学和传染病方面的工作表明，靶向给定器官内的不同细胞可以显著影响免疫应答的质量。在这里，我们研究了细胞水平的生物分布动力学后，管理超小普朗尼克稳定的聚（丙烯硫醚）纳米粒子在小鼠中。这些纳米颗粒依靠淋巴引流到达淋巴结和血液，然后进入脾脏而不是肝脏，在那里它们与单核细胞、巨噬细胞和骨髓树突状细胞相互作用。皮内注射（i.d.）与肌内给药相比，导致血液中的生物利用度增加约50%。当静脉注射时，它们的分布有利于抗原呈递细胞，特别是对髓样细胞的强靶向性。在荷瘤小鼠中，单核细胞和多形核细胞骨髓衍生的抑制细胞隔室被有效且优先靶向，使得这种纳米颗粒制剂可能用于逆转这些细胞在肿瘤基质中的高度抑制活性。
Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.
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影响因子：
6.2
作者：
Kang SM;Song JM;Kim YC
通讯作者：
Kim YC
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
DOI：
10.1073/pnas.0307124101
发表时间：
2004-01-06
影响因子：
11.1
作者：
Kang, YS;Kim, JY;Park, CG
通讯作者：
Park, CG
DOI：
10.1073/pnas.1105200108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Jewell, Christopher M.;Lopez, Sandra C. Bustamante;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
46.9
作者：
通讯作者：
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