<br>通过整合癌细胞膜和AS1411适配体对空心金纳米粒子进行表面修饰，旨在实现结直肠癌的双靶向治疗,International Journal of Pharmaceutics

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通过整合癌细胞膜和AS1411适配体对空心金纳米粒子进行表面修饰，旨在实现结直肠癌的双靶向治疗
International Journal of Pharmaceutics ( IF 5.3 ) Pub Date : 2024-03-23 , DOI: 10.1016/j.ijpharm.2024.124036
Sepideh Hassibian ₁ , Seyed Mohammad Taghdisi ₂ , Zahra Jamshidi ₃ , Ali Samie ₄ , Morteza Alinezhad Nameghi ₅ , Mersedeh Shayan ₃ , Naser Farrokhi ₁ , Mona Alibolandi ₆ , Mohammad Ramezani ₆ , Seyed Mohsen Dehnavi ₁ , Khalil Abnous ₆

Affiliation

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，例如在血液中的长期存在、精确的识别能力和逃避免疫反应。这项研究涉及仿生纳米颗粒的生产，特别是负载甲氨蝶呤（MTX）的空心金纳米颗粒（HGNP），并进一步涂覆癌细胞膜。然后用 AS1411 适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适体和C26癌细胞膜）而表现出对癌细胞的精确靶向性，并且表现出分布的均匀性。它还表现出对光热刺激的理想响应、药物的控制释放以及荧光成像的特殊特性。该系统由直径为 51.33 ± 5.70 nm 的球形 HGNP 组成，通过物理吸收方法有效负载 MTX。封装效率达到79.54%，负载效率达到38.21%。根据细胞毒性测定，靶向制剂在核仁素阳性细胞系 C26 中显示出约 45% 的显着死亡率。由于对癌细胞膜中发现的同源结合粘附分子进行了功能化过程以及 AS1411 适体的靶向能力，Apt-CCM-HG@MTX 在实验中证明了其靶向肿瘤和促进细胞摄取的显着增强。此外，在近红外辐射下，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劲。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，从而显着改善 MTX 的有效管理和结直肠癌患者的治疗。

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Surface modification of hollow gold nanoparticles conducted by incorporating cancer cell membrane and AS1411 aptamer, aiming to achieve a dual-targeted therapy for colorectal cancer

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 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 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.

更新日期：2024-03-23

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