The aim of our study was to prepare multifunctional, biocompatible nanoparticles for site-specific drug delivery. Hydrophilic nanoparticles with surface-adorned amine, carboxyl, or aldehyde groups, to be later used for bio-conjugation, were designed using phosphonomethyl iminodiacetic acid (PMIDA) as the coupling agent. These PMIDA-coated cobalt oxide nanoparticles (PMIDA-CoO) were further functionalized with folic acid (FA), using simple technique. The particles show excellent aqueous dispersion stability in physiological pH without any deterioration in hydrodynamic size. The cytotoxicity and internalization efficiency of these nanocarriers have been evaluated on folate receptor over expressed KB and folate receptor lower expressed KG1a cells. Anticancer drugs such as doxorubicin and methotrexate were successfully attached to the folic acid-decoded PMIDA-CoO nanoparticles by simple reactions. Anticancer drug-loaded nanoparticles (FA-PMIDA-CoO) exhibit elevated cytotoxicity and induce apoptosis in cancer cells, which were confirmed by flow cytometry. Fluorescence microscopy study shows the higher amount of internalization of the noncomplex by KB cells, which clearly demonstrated that cells overexpressing the human folate receptor internalized a higher level of these nanoparticles–folate conjugates than folate receptor-negative control cells.

中文翻译：

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使用膦酰基甲基亚氨基二乙酸接着叶酸对氧化钴纳米粒子进行表面修饰：一种用于靶向抗癌药物递送的生物相容性载体。

我们研究的目的是制备用于特定部位药物递送的多功能，生物相容性纳米颗粒。使用膦酰基甲基亚氨基二乙酸（PMIDA）作为偶联剂，设计了具有表面修饰的胺基，羧基或醛基的亲水纳米粒子，随后将其用于生物偶联。使用简单的技术，将这些PMIDA涂层的氧化钴纳米颗粒（PMIDA-CoO）进一步用叶酸（FA）进行功能化。该颗粒在生理pH下显示出优异的水分散体稳定性，而流体动力学尺寸没有任何恶化。这些纳米载体的细胞毒性和内在化效率已经评估了叶酸受体的表达量超过了KB，而叶酸受体的表达量降低了KG1a细胞。通过简单的反应，将抗癌药（如阿霉素和甲氨蝶呤）成功附着到叶酸解码的PMIDA-CoO纳米颗粒上。流式细胞仪证实，载有抗癌药物的纳米颗粒（FA-PMIDA-CoO）表现出较高的细胞毒性并诱导癌细胞凋亡。荧光显微镜研究显示，KB细胞对非复合物的内在化程度更高，这清楚地表明，与叶酸受体阴性对照细胞相比，过表达人叶酸受体的细胞内化了更高水平的这些纳米颗粒-叶酸结合物。