Chinnathambi Shanmugavel, Kumar Mahima, Dutta Basudeb, Subramani Karthikeyan, Kandasamy Saravanan, Kmiecik Sebastian, Vaijayanthi Thangavel, Pandian Ganesh N
Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto 606-8501, Japan.
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
ACS Appl Bio Mater. 2025 Jul 21;8(7):6397-6414. doi: 10.1021/acsabm.5c00887. Epub 2025 Jun 20.
Metal-organic frameworks (MOFs) are gaining attention as multifunctional nanomaterials for biomedical applications due to their porosity, tunable structure, and potential for molecular-level imaging. In this study, we synthesized green-emitting, water-dispersible manganese-based MOF (Mn-MOF) nanoparticles for live-cell imaging and investigated their interactions with human serum albumin (HSA). Spectroscopic analyses revealed high-affinity binding, with fluorescence quenching constants in the range of 10. A red shift in emission and circular dichroism data confirmed that HSA retained its native conformation, underscoring the structural compatibility of Mn-MOFs. Biocompatibility was assessed using HeLa, A549, and chondrocyte cell lines. Cytotoxicity assays showed high cell viability at moderate concentrations and early time points. Nanoparticle size (∼18 nm by DLS; <10 nm by TEM) likely facilitated cellular uptake while minimizing toxicity. Confocal microscopy and flow cytometry revealed efficient internalization via multiple endocytic pathways, with perinuclear localization and no significant morphological changes. However, higher concentrations decreased cell adhesion and viability, indicating a dose-dependent toxicity threshold. These results demonstrate that Mn-MOF nanoparticles maintain protein integrity and exhibit low cytotoxicity, supporting their potential as safe, effective platforms for live-cell imaging and targeted delivery in nanomedicine.
金属有机框架材料（MOFs）因其孔隙率、可调节结构以及分子水平成像潜力，作为用于生物医学应用的多功能纳米材料正受到关注。在本研究中，我们合成了用于活细胞成像的绿色发光、水分散性锰基MOF（Mn-MOF）纳米颗粒，并研究了它们与人血清白蛋白（HSA）的相互作用。光谱分析揭示了高亲和力结合，荧光猝灭常数在10的范围内。发射光谱的红移和圆二色性数据证实HSA保留了其天然构象，突出了Mn-MOFs的结构相容性。使用HeLa、A549和软骨细胞系评估了生物相容性。细胞毒性试验表明，在中等浓度和早期时间点细胞活力较高。纳米颗粒大小（动态光散射约为18 nm；透射电镜小于10 nm）可能促进了细胞摄取，同时将毒性降至最低。共聚焦显微镜和流式细胞术显示通过多种内吞途径有效内化，具有核周定位且无明显形态变化。然而，较高浓度会降低细胞粘附和活力，表明存在剂量依赖性毒性阈值。这些结果表明，Mn-MOF纳米颗粒保持蛋白质完整性并表现出低细胞毒性，支持它们作为纳米医学中活细胞成像和靶向递送的安全、有效平台的潜力。
