Hassibian Sepideh, Taghdisi Seyed Mohammad, Jamshidi Zahra, Samie Ali, Alinezhad Nameghi Morteza, Shayan Mersedeh, Farrokhi Naser, Alibolandi Mona, Ramezani Mohammad, Dehnavi Seyed Mohsen, Abnous Khalil
Department of Cell and Molecular Biology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, P.O. Box 19839-69411, Tehran, Iran.
Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Pharm. 2024 Apr 25;655:124036. doi: 10.1016/j.ijpharm.2024.124036. Epub 2024 Mar 23.
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.
由于其固有的膜结构，被活性细胞膜包裹的纳米结构具有独特的特性，如在血液中存在时间延长、精确识别能力和逃避免疫反应。本研究涉及仿生纳米颗粒的制备，具体为负载甲氨蝶呤（MTX）的中空金纳米颗粒（HGNPs），并进一步用癌细胞膜包覆。然后用AS1411适配体修饰这些纳米颗粒作为靶向剂（Apt-CCM-HG@MTX）。该纳米平台由于其双靶向特性（AS1411适配体和C26癌细胞膜）而表现出对癌细胞的精确靶向，分布均匀。它还对光热刺激表现出理想的响应、药物的控释以及荧光成像的优异性能。该系统由直径为51.33±5.70nm的球形HGNPs组成，采用物理吸附法有效地负载了MTX。所达到的包封率记录为79.54%，而负载率达到38.21%。通过体外细胞毒性试验测定，靶向制剂在核仁素阳性细胞系C26中显示出约45%的显著死亡率。由于对癌细胞膜中发现的同源结合粘附分子应用了功能化过程以及AS1411适配体的靶向能力，Apt-CCM-HG@MTX在体内实验中显示出在靶向肿瘤和促进细胞摄取方面有显著增强。此外，在近红外辐射下，由于HGNPs的独特属性，Apt-CCM-HG@MTX在肿瘤区域表现出的光热效应非常显著。本研究得出的结论有可能有助于采用一种受生物启发的策略，这将显著改善MTX的有效管理以及对结直肠癌患者的治疗。
