School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112521. doi: 10.1016/j.msec.2021.112521. Epub 2021 Oct 26.
Efficient and selective targeting of inflamed tissues/organs is critical for diagnosis and therapy. Although nanomaterials themselves have an intrinsic advantage due to their size for targeting inflammation sites, additional functionalization of the nanomaterials with proper targeting moieties is desired to enhance the targeting efficiency. In this study, we aimed to improve the inflammation targeting characteristics of a pluronic-based nanocarrier, which has advantages as a nanosized delivery cargo for diverse molecules, by conjugating with chitosan and ZnBPMP (two Zn(II) ions chelated 2,6-bis[(bis(2-pyridylmethyl)amino)-methyl]-4-methylphenol) moiety. Specific and significant cellular uptake and interaction between the nanocarrier functionalized with ZnBPMP ligand and chitosan to an apoptosis-induced immune cell line were observed in vitro. An inflammation model in the mouse ear caused by skin hypersensitivity was used to evaluate the effect of functionalization with chitosan and ZnBPMP moiety by comparing with various control groups. Functionalization of the nanocarrier with chitosan greatly enhanced the in vivo circulation time of the nanocarrier, so prolonged targeting ability of the nanocarrier to the inflamed ear was achieved. Additional ZnBPMP functionalization to chitosan-functionalized nanocarrier also resulted in significantly improved initial targeting and further enhancement in the targeting until 5 days to the inflamed ear and the decreased non-specific accumulation of the nanocarrier to the remaining body. Thus, developed nanocarrier has a high potential as a drug delivery carrier as well as a diagnostic agent to the inflammation sites.
高效且选择性地靶向炎症组织/器官对于诊断和治疗至关重要。尽管纳米材料本身由于其尺寸而具有靶向炎症部位的固有优势，但仍需要对纳米材料进行适当的靶向配体功能化，以提高靶向效率。在这项研究中，我们旨在通过与壳聚糖和 ZnBPMP（两个锌（II）离子螯合 2,6-双[（双（2-吡啶基甲基）氨基）甲基]-4-甲基苯酚）部分缀合，来改善基于普朗尼克的纳米载体的炎症靶向特性。该纳米载体作为各种分子的纳米级递送载体具有优势，我们观察到与壳聚糖和 ZnBPMP 配体缀合的纳米载体在体外与凋亡诱导免疫细胞系的特异性和显著的细胞摄取和相互作用。使用皮肤过敏引起的小鼠耳部炎症模型，通过与各种对照组进行比较，评估了壳聚糖和 ZnBPMP 部分功能化的效果。壳聚糖功能化的纳米载体大大延长了纳米载体在体内的循环时间，从而实现了对炎症耳朵的延长靶向能力。此外，壳聚糖功能化的纳米载体上的 ZnBPMP 功能化也导致对炎症耳朵的初始靶向显著改善，并进一步增强至 5 天，同时减少了纳米载体对剩余身体的非特异性积累。因此，开发的纳米载体具有作为药物递送载体以及炎症部位诊断剂的高潜力。
