Abstract

Nanoparticles (NPs) with ‘stealth’ properties have been designed to decrease the phagocytosis of such particles by mononuclear phagocytes and to protect them from enzymatic degradation, thus improving circulation time and bioavailability after intravenous administration. Brain-targeting modifications endow NPs with the capacity to cross the blood–brain barrier, facilitating chemotherapy for brain diseases such as glioma. In this study, newly designed alkoxy cyanoacrylate (CA)-based NPs with stealth and brain-targeting properties were synthesised and evaluated. The monomers for NP core polymerisation were chemically modified to hydrophilic short alkoxy structure for stealth purposes and coated with polysorbate-80 for brain targeting. Two monomers (2-methoxyethyl CA and 2-(2-methoxyethyl)ethyl CA) were used to create NP₂ and NP₃, respectively. Both NPs were successfully loaded with anti-sense oligonucleotide (ASON) of transforming growth factor beta 2. Compared to traditional n-butyl CA-based ASON–NP₁, ASON–NP₃ was found to decrease phagocytosis by mononuclear macrophages (RAW264.7) and to increase cellular uptake by cancer cells. ASON–NP₃ showed definite brain targeting and anti-cancer effects. This work provides a potential new strategy for preparing stealth NPs core, providing a new NP vehicle for clinical drug delivery that may be targeted to the brain and circulates in the blood for an extended period of time.

摘要

具有“隐形”特性的纳米颗粒 (NPs) 旨在减少单核吞噬细胞对此类颗粒的吞噬作用并保护它们免受酶降解，从而改善静脉内给药后的循环时间和生物利用度。脑靶向修饰赋予 NPs 穿过血脑屏障的能力，促进脑疾病（如胶质瘤）的化疗。在这项研究中，合成并评估了新设计的具有隐身和脑靶向特性的基于烷氧基氰基丙烯酸酯 (CA) 的纳米粒子。用于 NP 核心聚合的单体被化学改性为亲水性短烷氧基结构以用于隐形目的，并涂有聚山梨醇酯 80 用于脑靶向。使用两种单体（2-甲氧基乙基 CA 和 2-（2-甲氧基乙基）乙基 CA）来产生 NP ₂和NP ₃，分别。两种 NP 均成功装载了转化生长因子 β 2 的反义寡核苷酸 (ASON)。与传统的基于正丁基 CA 的 ASON-NP ₁相比，发现 ASON-NP ₃可降低单核巨噬细胞的吞噬作用 (RAW264.7 ) 并增加癌细胞对细胞的吸收。ASON-NP ₃显示出明确的脑靶向和抗癌作用。这项工作为制备隐形 NPs 核心提供了一种潜在的新策略，为临床药物递送提供了一种新的 NP 载体，该载体可以靶向大脑并在血液中循环较长时间。