Gao Han, Cheng Ruoyu, Cardoso Inês, Lobita Maria, Pacheco-Fernández Idaira, Bártolo Raquel, Rodrigues Lígia R, Hirvonen Jouni, A Santos Hélder
Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Nano Lett. 2025 Feb 19;25(7):2831-2840. doi: 10.1021/acs.nanolett.4c05999. Epub 2025 Feb 6.
The immune system safeguards as primary defense by recognizing nanomaterials and maintaining homeostasis, gaining a deeper understanding of these interactions may change the treating paradigm of immunotherapy. Here, we adopted copper as the principal component of nanoparticles (NPs), given its features of coordination with different benezenecarboxylate ligands to form metal-organic frameworks and complexes with distinct morphologies. As a result, four types of shape-tunable copper-coordinated NPs (CuCNPs) are developed: cuboctahedron, needle, octahedron, and plate NPs. Biocompatibility of CuCNPs varies across different cell lines (RAW264.7, THP-1, HEK 293 and HeLa) in a shape-dependent manner, with needle-shaped CuCNPs showing pronounced cytotoxicity (IC50:104.3 μg mL at 24 h). Among different shapes, a notable increase of 8.47% in the CD206 subpopulations is observed in needle-shaped CuCNPs, followed by 77% enhancement at 48 h. Overall, this study underscores the shape-dependent immune-regulatory effects of CuCNPs and sheds light on the rational design of nanoscale metal complexes for potential immunotherapy.
免疫系统通过识别纳米材料并维持体内平衡来提供主要防御，深入了解这些相互作用可能会改变免疫治疗的治疗模式。在此，我们采用铜作为纳米颗粒（NPs）的主要成分，因为其具有与不同苯甲酸酯配体配位形成具有不同形态的金属有机框架和配合物的特性。结果，开发出了四种形状可调的铜配位NPs（CuCNPs）：立方八面体、针状、八面体和片状NPs。CuCNPs的生物相容性在不同细胞系（RAW264.7、THP-1、HEK 293和HeLa）中呈现出形状依赖性变化，针状CuCNPs表现出明显的细胞毒性（24小时时IC50为104.3μg/mL）。在不同形状中，针状CuCNPs的CD206亚群显著增加了8.47%，48小时时增加了77%。总体而言，本研究强调了CuCNPs的形状依赖性免疫调节作用，并为潜在免疫治疗的纳米级金属配合物的合理设计提供了思路。
