Critical Size Limit of Biodegradable Nanoparticles for Enhanced Lymph Node Trafficking and Paracortex Penetration.
Critical Size Limit of Biodegradable Nanoparticles for Enhanced Lymph Node Trafficking and Paracortex Penetration.
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可生物降解的纳米颗粒的临界尺寸极限，用于增强淋巴结运输和副型穿透性。
DOI：
10.1007/s12274-019-2301-3
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发表时间：
2019-04
期刊：
影响因子：
9.9
通讯作者：
Mao HQ
中科院分区：
文献类型：
--
作者：
Howard GP;Verma G;Ke X;Thayer WM;Hamerly T;Baxter VK;Lee JE;Dinglasan RR;Mao HQ
通过纳米粒子 (NP) 间质引流靶向淋巴结 (LN) 是刺激有效免疫反应的一种有吸引力的策略，因为 LN 是抗原呈递细胞 (APC) 启动淋巴细胞并触发适应性免疫反应的主要部位。 NP 大小已被证明会影响皮下注射后 LN 靶向和保留的效率。对于临床转化，可生物降解的纳米粒子是疫苗递送的首选载体。然而，有效液氮排放的选择性“尺寸门”，特别是液氮运输的动力学，尚不明确。这部分是由于从亚 100 纳米范围内的可生物降解聚合物生成尺寸受控的纳米粒子的挑战。在这里，我们报告了使用闪蒸纳米沉淀法制备了三组聚（乳酸-共-乙醇）-b-聚（乙二醇）（PLGA-b-PEG）纳米颗粒，数均直径分别为20、40和100纳米，尺寸分布窄。使用近红外染料标记的纳米颗粒，我们发现，在小鼠皮下接种后，20纳米纳米颗粒可以快速穿过近端和远端淋巴结，并且比数均直径为40纳米的纳米颗粒更有效地保留在淋巴结中。 100 nm 纳米颗粒的流失可以忽略不计。此外，20 nm 纳米粒子在副皮质区域周围表现出最高程度的渗透，并且增强了对 LN 中树突状细胞的接触。总之，这些数据证实，约 30 nm 下限的小型、尺寸控制的 PLGA-b-PEG NP 对于皮下注射后的 LN 运输、保留和 APC 摄取最有效。行政。该报告可以为用于递送治疗性或预防性疫苗的 LN 靶向 NP 载体的设计提供信息。筛选了具有窄尺寸分布的可生物降解的 PEG-b-PLGA 纳米粒子用于淋巴结靶向，证明 20 nm 纳米粒子在 24 小时内增强了主要引流淋巴结的引流和保留。
Lymph node (LN) targeting through interstitial drainage of nanoparticles (NPs) is an attractive strategy to stimulate a potent immune response, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective “size gate” for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol) (PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retained in LNs more effectively than NPs with a number average diameter of 40-nm. The drainage of 100-nm NPs was negligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines. Biodegradable PEG-b-PLGA nanoparticles with narrow size distributions were screened for lymph node targeting, demonstrating that 20-nm nanoparticles have enhanced drainage and retention in the major draining lymph nodes over a 24 h period.
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影响因子：
4.6
作者：
Tomura M;Hata A;Matsuoka S;Shand FH;Nakanishi Y;Ikebuchi R;Ueha S;Tsutsui H;Inaba K;Matsushima K;Miyawaki A;Kabashima K;Watanabe T;Kanagawa O
通讯作者：
Kanagawa O
影响因子：
6.6
作者：
Thomas SN;Schudel A
通讯作者：
Schudel A
影响因子：
2.2
作者：
Harrell, Maria I.;Iritani, Brian M.;Ruddell, Alanna
通讯作者：
Ruddell, Alanna
DOI：
10.1073/pnas.1408686111
发表时间：
2015-01-13
影响因子：
11.1
作者：
Maldonado, Roberto A.;LaMothe, Robert A.;Kishimoto, Takashi Kei
通讯作者：
Kishimoto, Takashi Kei
影响因子：
3.3
作者：
Reddy, Sai T.;Berk, David A.;Swartz, Melody A.
通讯作者：
Swartz, Melody A.