肽包覆聚己内酯-苯扎氯铵纳米胶囊用于胰腺β细胞靶向给药

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-10-21 Epub Date: 2024-09-24 DOI:10.1021/acsabm.4c00621
Jillian Collins, Jessie M Barra, Keifer Holcomb, Andres Ocampo, Ashton Fremin, Austin Kratz, Jubril Akolade, Julianna K Hays, Ali Shilleh, Amit Sela, David J Hodson, Johannes Broichhagen, Holger A Russ, Nikki L Farnsworth
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引用次数: 0

摘要

将目前治疗或预防一型糖尿病(T1D)患者胰岛β细胞丢失的疗法作为靶点,可提高疗效并减少脱靶效应。由于缺乏β细胞特异性靶点,而且无法用同一种给药载体测试多种靶向分子,目前靶向β细胞的努力受到了限制。在这里,我们制作了一种可定制的聚己内酯纳米胶囊(NC),其中可互换连接多种不同的靶向肽,以实现β细胞特异性递送。在 NC 外壳中加入阳离子表面活性剂后,就能附着 Exendin-4 和外核苷酸三磷酸二氢水解酶 3 (ENTPD3) 抗体,实现 β 细胞特异性靶向。NC 的平均尺寸为 250 至 300 nm,多分散指数低于 0.2。这种 NC 无毒,在培养基中稳定,可以冻干和重组。涂有靶向肽的NCs在体外被人类胰岛β细胞和人类干细胞衍生的β样细胞(sBC)吸收,具有高度的特异性。此外,NCs 还成功地将疏水性和亲水性货物输送到人类 β 细胞。此外,Exendin-4包被的NCs是稳定的,并能在体内靶向小鼠胰岛β细胞。总之,我们的可定制 NCs 具有改善细胞靶向给药的潜力,可用作测试细胞靶向肽功效的筛选平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell.

Targeting current therapies to treat or prevent the loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off-target effects. Current efforts to target the β-cell are limited by a lack of β-cell-specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here, we fabricate a tailorable polycaprolactone nanocapsule (NC) in which multiple different targeting peptides can be interchangeably attached for β-cell-specific delivery. Incorporation of a cationic surfactant in the NC shell allows for the attachment of Exendin-4 and an antibody for ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) for β-cell-specific targeting. The average NC size ranges from 250 to 300 nm with a polydispersity index under 0.2. The NCs are nontoxic, stable in media culture, and can be lyophilized and reconstituted. NCs coated with a targeting peptide were taken up by human cadaveric islet β-cells and human stem cell-derived β-like cells (sBC) in vitro with a high level of specificity. Furthermore, NCs successfully delivered both hydrophobic and hydrophilic cargo to human β-cells. Additionally, Exendin-4-coated NCs were stable and targeted the mouse pancreatic islet β-cell in vivo. Overall, our tailorable NCs have the potential to improve cell-targeted drug delivery and can be utilized as a screening platform to test the efficacy of cell-targeting peptides.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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