Abstract：
Due to its inherent membrane structure, a nanostructure enveloped by an active cell membrane possesses distinctive characteristics such as prolonged presence in the bloodstream, precise identification capabilities, and evasion of immune responses. This research involved the production of biomimetic nanoparticles, specifically hollow gold nanoparticles (HGNPs) loaded with methotrexate (MTX), which were further coated with cancer cell membrane. These nanoparticles were then adorned with AS1411 aptamer to serve as a targeting agent (Apt-CCM-HG@MTX). The nanoplatform demonstrated precise targeting towards cancer cells due to its dual-targeting characteristic (AS1411 aptamer and C26 cancer cell membrane), exhibiting uniformity in distribution. It also displayed a desirable response to photothermal stimulation, controlled release of drugs, and exceptional properties for fluorescence imaging. The system was composed of spherical HGNPs measuring 51.33 ± 5.70 nm in diameter, which were effectively loaded with MTX using a physical absorption method. The encapsulation efficiency achieved was recorded at 79.54 %, while the loading efficiency reached 38.21 %. The targeted formulation demonstrated a noteworthy mortality of approximately 45 % in the nucleolin positive cell line, C26, as determined by in vitro cytotoxicity assays. As a result of the functionalization process applied to the homologous binding adhesion molecules found in cancer cell membranes and targeting ability of AS1411 aptamer, Apt-CCM-HG@MTX demonstrated a substantial enhancement in targeting tumors and facilitating cellular uptake during in vivo experiments. Furthermore, under NIR radiation the photothermal effect exhibited by Apt-CCM-HG@MTX in the tumor area was notably robust due to the distinctive attributes of HGNPs. The conclusions obtained from this study have the potential to assist in adopting a bioinspired strategy that will significantly improve the effective management of MTX and therapy for individuals with colorectal cancer.
摘要：
由于其固有的膜结构，由活性细胞膜包裹的纳米结构具有独特的特征，例如在血液中长时间存在，精确的识别能力，和逃避免疫反应。这项研究涉及仿生纳米粒子的生产，特别是负载有甲氨蝶呤（MTX）的中空金纳米颗粒（HGNPs），进一步涂有癌细胞膜。然后用AS1411适体装饰这些纳米颗粒以用作靶向剂(Apt-CCM-HG@MTX)。由于其双重靶向特性（AS1411适体和C26癌细胞膜），纳米平台表现出对癌细胞的精确靶向。表现出分布的均匀性。它还显示了对光热刺激的理想反应，药物的控释，和特殊的荧光成像性能。该系统由直径为51.33±5.70nm的球形HGNP组成，使用物理吸收方法有效地加载了MTX。获得的包封效率记录为79.54%，加载效率达到38.21%。靶向制剂在核仁素阳性细胞系中表现出显著的约45%的死亡率。C26,如通过体外细胞毒性测定所确定的。由于应用于癌细胞膜中发现的同源结合粘附分子的功能化过程和AS1411适体的靶向能力，在体内实验期间,Apt-CCM-HG@MTX在靶向肿瘤和促进细胞摄取方面表现出显著增强。此外，在NIR辐射下，由于HGNP的独特属性，Apt-CCM-HG@MTX在肿瘤区域表现出的光热效应非常强大。从这项研究中获得的结论有可能有助于采用生物启发策略，该策略将显着改善对结直肠癌患者的MTX和治疗的有效管理。
