pH-responsive nanoparticles are ideal vehicles for drug delivery and are widely used in cell imaging in targeted therapy of cancer, which usually has a weakly acidic microenvironment. In this work, we constructed a titratable molecular model for nanoparticles grafted with ligands of pH-sensitive carboxylic acids and investigated the interactions between the nanoparticles and the lipid bilayer in varying pH environments. We mainly examined the effect of the grafting density of the pH-sensitive ligands of the nanoparticles on the interactions of the nanoparticles with the lipid bilayer. The results show that the nanoparticles can penetrate the lipid bilayer only when the pH value is lower than a critical value, which can be readily modulated to the specific pH value of the tumor microenvironment by changing the ligand grafting density. This work provides some insights into modulating the interactions between the pH-sensitive nanoparticles and cellular membranes to realize targeted drug delivery to tumors based on their specific pH environment.

中文翻译：

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使用可滴定马提尼模型揭示肿瘤靶向纳米颗粒与脂质双层的相互作用

pH响应纳米颗粒是理想的药物输送载体，广泛应用于癌症靶向治疗的细胞成像，而癌症通常具有弱酸性微环境。在这项工作中，我们构建了接枝有 pH 敏感羧酸配体的纳米颗粒的可滴定分子模型，并研究了不同 pH 环境下纳米颗粒与脂质双层之间的相互作用。我们主要研究了纳米粒子pH敏感配体的接枝密度对纳米粒子与脂质双层相互作用的影响。结果表明，纳米粒子只有在pH值低于临界值时才能穿透脂质双层，并且可以通过改变配体接枝密度轻松调节到肿瘤微环境的特定pH值。这项工作为调节 pH 敏感纳米粒子和细胞膜之间的相互作用提供了一些见解，以根据肿瘤的特定 pH 环境实现靶向药物递送。