Shear-Resistant, Biological Tethering of Nanostimulators for Enhanced Therapeutic Cell Paracrine Factor Secretion.
Shear-Resistant, Biological Tethering of Nanostimulators for Enhanced Therapeutic Cell Paracrine Factor Secretion.
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DOI：
10.1021/acsami.1c01520
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发表时间：
2021-04-21
影响因子：
9.5
通讯作者：
Kong, Hyunjoon
中科院分区：
文献类型：
--
作者：
Hong, Yu-Tong;Teo, Jye Yng;Jeon, Hojeong;Kong, Hyunjoon
关键词：
间充质基质细胞(MSCs)能分泌多种生长因子和免疫调节细胞因子，在再生医学领域具有广阔的应用前景。为了进一步增强它们的分泌活性，已经出现了通过形成非化学键将纳米尺寸的分泌刺激载体(称为纳米刺激剂)拴在MSC表面的努力。尽管取得了一些成功，但在通过注射器针运输纳米刺激物的过程中，仍有很大的需要改善纳米刺激剂的保留率，在注射器针中，细胞表面施加的高剪应力将它们分开。为此，我们假设聚乳酸-羟基乙酸嵌段透明质酸(PLGA-HA)与整合素结合的RGD多肽(PLGA-HA-RGD)可以形成纳米刺激物，并在注射过程中稳定地留在细胞表面。由此形成的HA-CD44和RGD-整合素键将协同增加纳米刺激剂的黏附强度。有趣的是，用PLGA-HA-RGD制备的纳米刺激剂的保留率是用PLGA-HA制备的纳米刺激剂的3-6倍。因此，PLGA-HA-RGD纳米刺激剂诱导MSCs分泌比PLGA-HA纳米刺激剂高1.5倍的血管内皮生长因子和1.2倍的基质金属蛋白酶-1组织抑制因子。因此，与PLGA-HA-RGD纳米刺激剂捆绑的MSCs可以刺激内皮细胞的活性，形成血管样内皮腔，连接长度和数量增加。纳米刺激器设计策略也将广泛适用于通过将载体与感兴趣的生物活性分子捆绑在一起来调节、保护和安置广泛的治疗或免疫细胞。
Mesenchymal stromal cells (MSCs) secreting multiple growth factors and immunomodulatory cytokines are promising for regenerative medicine. To further enhance their secretory activity, efforts have emerged to tether nanosized carriers of secretory stimuli, named nanostimulators, to the MSC surface by forming nonchemical bonds. Despite some successes, there is a great need to improve the retention of nanostimulators during transport through a syringe needle, where high shear stress exerted on the cell surface separates them. To this end, we hypothesize that poly(lactic-co-glycolic acid)-block-hyaluronic acid (PLGA-HA) conjugated with integrin-binding RGD peptides, denoted PLGA-HA-RGD, can form nanostimulators that remain on the cell surface stably during the injection. The resulting HA-CD44 and RGD-integrin bonds would synergistically increase the adhesion strength of nanostimulators. Interestingly, nanostimulators prepared with PLGA-HA-RGD show 3- to 6-fold higher retention than those made with PLGA-HA. Therefore, the PLGA-HA-RGD nanostimulators induced MSCs to secrete 1.5-fold higher vascular endothelial growth factors and a 1.2-fold higher tissue inhibitor of matrix metalloproteinase-1 as compared to PLGA-HA nanostimulators. Consequently, MSCs tethered with PLGA-HA-RGD nanostimulators served to stimulate endothelial cell activities to form a blood vessel-like endothelial lumen with increased length and number of junctions. The nanostimulator design strategy would also be broadly applicable to regulate, protect, and home a broad array of therapeutic or immune cells by tethering carriers with bioactive molecules of interest.
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影响因子：
17.1
作者：
Leong J;Hong YT;Wu YF;Ko E;Dvoretskiy S;Teo JY;Kim BS;Kim K;Jeon H;Boppart M;Yang YY;Kong H
通讯作者：
Kong H
影响因子：
9.7
作者：
Dicker, Kevin T.;Gurski, Lisa A.;Pradhan-Bhatt, Swati;Witt, Robert L.;Farach-Carson, Mary C.;Jia, Xinqiao
通讯作者：
Jia, Xinqiao
影响因子：
7.4
作者：
Mamidi MK;Singh G;Husin JM;Nathan KG;Sasidharan G;Zakaria Z;Bhonde R;Majumdar AS;Das AK
通讯作者：
Das AK
影响因子：
3.7
作者：
Barnes, J. Matthew;Nauseef, Jones T.;Henry, Michael D.
通讯作者：
Henry, Michael D.
影响因子：
4.9
作者：
Digilio, Giuseppe;Catanzaro, Valeria;Aime, Silvio
通讯作者：
Aime, Silvio