Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell.

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

Abstract

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.

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
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。
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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
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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