Weiss Adam M, Macke Nicholas, Zhang Yefei, Calvino Céline, Esser-Kahn Aaron P, Rowan Stuart J
Department of Chemistry, University of Chicago 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.
Pritzker School of Molecular Engineering, University of Chicago 5640 South Ellis Avenue, Chicago, Illinois 60637, United States.
ACS Biomater Sci Eng. 2021 Apr 12;7(4):1450-1461. doi: 10.1021/acsbiomaterials.0c01618. Epub 2021 Mar 9.
Cellulose nanocrystals (CNCs) are an emergent, sustainable nanomaterial that are biosourced, abundant, and biodegradable. On account of their high aspect ratio, low density, and mechanical rigidity, they have been employed in numerous areas of biomedical research including as reinforcing materials for bone or tissue scaffolds or as carriers in drug delivery systems. Given the promise of these materials for such use, characterizing and understanding their interactions with biological systems is an important step to prevent toxicity or inflammation. Reported herein are studies aimed at exploring the and effects that the source, length, and charge of the CNCs have on cytotoxicity and immune response. CNCs from four different biosources (cotton, wood, , and sea tunicate) were prepared and functionalized with positive or negative charges to obtain a small library of CNCs with a range of dimensions and surface charge. A method to remove endotoxic or other impurities on the CNC surface leftover from the isolation process was developed, and the biocompatibility of the CNCs was subsequently assayed and After subcutaneous injection, it was found that unfunctionalized (uncharged) CNCs form aggregates at the site of injection, inducing splenomegaly and neutrophil infiltration, while charged CNCs having surface carboxylates, sulfate half-esters, or primary amines were biologically inert. No effect of the particle source or length was observed in the and studies conducted. The lack of an or immune response toward charged CNCs in these experiments supports their use in future biological studies.
纤维素纳米晶体(CNCs)是一种新兴的、可持续的纳米材料,其来源于生物、储量丰富且可生物降解。由于其高长径比、低密度和机械刚性,它们已被应用于生物医学研究的众多领域,包括作为骨或组织支架的增强材料,或作为药物递送系统中的载体。鉴于这些材料在此类应用中的前景,表征和了解它们与生物系统的相互作用是预防毒性或炎症的重要一步。本文报道的研究旨在探索CNCs的来源、长度和电荷对细胞毒性和免疫反应的影响。制备了来自四种不同生物来源(棉花、木材、 和海鞘)的CNCs,并对其进行正电荷或负电荷功能化处理,以获得一系列具有不同尺寸和表面电荷的CNCs文库。开发了一种去除分离过程中残留在CNC表面的内毒素或其他杂质的方法,随后对CNCs的生物相容性进行了测定 和 皮下注射后发现,未功能化(不带电荷)的CNCs在注射部位形成聚集体,导致脾肿大和中性粒细胞浸润,而具有表面羧酸盐、硫酸半酯或伯胺的带电CNCs则具有生物惰性。在进行的 和 研究中未观察到颗粒来源或长度的影响。这些实验中对带电CNCs缺乏 或 免疫反应,支持了它们在未来生物学研究中的应用。