Lung cancer is one of the most frequently diagnosed cancers all over the world and is also one of the leading causes of cancer-related mortality. The main treatment option for small cell lung cancer, conventional chemotherapy, is characterized by a lack of specificity, resulting in severe adverse effects. Therefore, this study aimed at developing a new targeted drug delivery (TDD) system based on Ag–In–Zn–S quantum dots (QDs). For this purpose, the QD nanocrystals were modified with 11-mercaptoundecanoic acid (MUA), L-cysteine, and lipoic acid decorated with folic acid (FA) and used as a novel TDD system for targeting doxorubicin (DOX) to folate receptors (FARs) on adenocarcinomic human alveolar basal epithelial cells (A549). NIH/3T3 cells were used as FAR-negative controls. Comprehensive physicochemical, cytotoxicity, and genotoxicity studies were performed to characterize the developed novel TDDs. Fourier transformation infrared spectroscopy, dynamic light scattering, and fluorescence quenching confirmed the successful attachment of FA to the QD nanocrystals and of DOX to the QD–FA nanocarriers. UV–Vis analysis helped in determining the amount of FA and DOX covalently anchored to the surface of the QD nanocrystals. Biological screening revealed that the QD–FA–DOX nanoconjugates had higher cytotoxicity in comparison to the other forms of synthesized QD samples, suggesting the cytotoxic effect of DOX liberated from the QD constructs. Contrary to the QD–MUA–FA–DOX nanoconjugates which occurred to be the most cytotoxic against A549 cells among others, no such effect was observed for NIH/3T3 cells, confirming FARs as molecular targets. In vitro scratch assay also revealed significant inhibition of A549 cell migration after treatment with QD–MUA–FA–DOX. The performed studies evidenced that at IC50 all the nanoconjugates induced significantly more DNA breaks than that observed in nontreated cells. Overall, the QD–MUA–FA–DOX nanoconjugates showed the greatest cytotoxicity and genotoxicity, while significantly inhibiting the migratory potential of A549 cells. QD–MUA–FA–DOX nanoconjugates can thus be considered as a potential drug delivery system for the effective treatment of adenocarcinomic human alveolar basal epithelial cells.

中文翻译：

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量子点作为靶向的阿霉素药物递送纳米系统

肺癌是全世界最常被诊断的癌症之一，也是癌症相关死亡率的主要原因之一。小细胞肺癌的主要治疗选择是常规化疗，其特点是缺乏特异性，导致严重的不良反应。因此，本研究旨在开发一种基于Ag-In-Zn-S量子点（QD）的新型靶向药物递送（TDD）系统。为此，用11-巯基十一烷酸（MUA），L-半胱氨酸和叶酸（FA）修饰的硫辛酸修饰QD纳米晶体，并将其用作将阿霉素（DOX）靶向至叶酸受体（FARs）的新型TDD系统）在腺癌的人肺泡基底上皮细胞（A549）上。NIH / 3T3细胞用作FAR阴性对照。全面的理化，细胞毒性，进行了遗传毒性研究以表征已开发的新型TDD。傅里叶变换红外光谱，动态光散射和荧光猝灭证实了FA成功附着于QD纳米晶体，DOX成功附着于QD–FA纳米载体。UV-Vis分析有助于确定共价锚定在QD纳米晶体表面的FA和DOX的数量。生物筛选显示，与其他形式的合成QD样品相比，QD–FA–DOX纳米共轭物具有更高的细胞毒性，表明从QD构建体中释放出的DOX的细胞毒性作用。与QD–MUA–FA–DOX纳米缀合物相反，纳米缀合物对A549细胞的杀伤力最大，对NIH / 3T3细胞未观察到这种作用，证实了FARs是分子靶标。体外刮擦试验还显示，用QD–MUA–FA–DOX处理后，A549细胞迁移受到显着抑制。进行的研究证明，在IC50时，所有纳米偶联物诱导的DNA断裂数量均比未处理细胞明显多。总体而言，QD–MUA–FA–DOX纳米偶联物显示出最大的细胞毒性和遗传毒性，同时显着抑制了A549细胞的迁移潜能。因此，可以将QD–MUA–FA–DOX纳米缀合物视为有效治疗腺癌人类肺泡基底上皮细胞的潜在药物递送系统。QD–MUA–FA–DOX纳米偶联物显示出最大的细胞毒性和遗传毒性，同时显着抑制了A549细胞的迁移潜能。因此，可以将QD–MUA–FA–DOX纳米缀合物视为有效治疗腺癌人类肺泡基底上皮细胞的潜在药物递送系统。QD–MUA–FA–DOX纳米偶联物显示出最大的细胞毒性和遗传毒性，同时显着抑制了A549细胞的迁移潜能。因此，可以将QD–MUA–FA–DOX纳米缀合物视为有效治疗腺癌人类肺泡基底上皮细胞的潜在药物递送系统。