Nanoparticles are the new entities that can greatly limit the various side effects of systemic chemotherapy, and that coupled with a targeting moiety enables site-specific delivery of drugs. Folate receptors are overexpressed in retinoblastoma cells, thus these can specifically uptake the drug-loaded nanoparticles, thereby increasing the cytotoxicity at the tumor site. In our work, doxorubicin-loaded chitosan nanoparticles was prepared and then conjugated to folic acid. The conjugation efficiency was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Thereafter, the efficacy of FA-conjugated DOX-CNPs on retinoblastoma cells (Y-79) was analyzed by MTT assay which demonstrated superior cytotoxic effects as compared to unconjugated DOX-CNPs and native DOX. This may be due to enhanced intracellular uptake of DOX-CNPs-FA (30%) than that of DOX-CNPs (13.24%) and native DOX (5.01%), resulting from the high affinity of FA for folate receptors. Finally, the mechanism of doxorubicin-mediated apoptosis in retinoblastoma cell line (Y-79) was investigated which demonstrated that the mitochondrial pathway is activated and that the FA-conjugated DOX-CNPs are most effective and causes enhanced release of cytochrome c as well as the activation of downstream caspases to assist in apoptosis. Thus, the FA-targeted NPs were proved to possess sustainable, controlled, and targeted delivery of anticancer drugs with DOX as a model drug, which may provide a drug delivery system of precise control and targeting effect for the treatment of retinoblastoma.

中文翻译：

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叶酸修饰的壳聚糖纳米粒靶向递送至成视网膜细胞瘤中，评价阿霉素的细胞毒性和凋亡机制。

纳米颗粒是可以极大地限制全身化学疗法的各种副作用的新实体，并且与靶向部分结合可以实现药物的定点递送。叶酸受体在成视网膜细胞瘤细胞中过表达，因此它们可以特异性地摄取载有药物的纳米颗粒，从而增加肿瘤部位的细胞毒性。在我们的工作中，制备了负载阿霉素的壳聚糖纳米粒子，然后将其与叶酸偶联。通过核磁共振和傅立叶变换红外光谱表征了缀合效率。此后，通过MTT分析法分析了FA缀合的DOX-CNP对成视网膜细胞瘤细胞（Y-79）的功效，与未缀合的DOX-CNP和天然DOX相比，FAT缀合的DOX-CNP具有更好的细胞毒性作用。这可能是由于FA对叶酸受体的高亲和力导致DOX-CNPs-FA（30％）比DOX-CNPs（13.24％）和天然DOX（5.01％）的细胞内摄取增强。最后，研究了阿霉素介导的视网膜母细胞瘤细胞系（Y-79）凋亡的机制，这表明线粒体途径被激活，FA偶联的DOX-CNP最有效，并导致细胞色素c的释放增强。下游胱天蛋白酶的活化以协助细胞凋亡。因此，以DOX为模型药物，证明了以FA为靶标的NP具有可持续，可控和靶向的抗癌药物递送，这可以为治疗成视网膜细胞瘤提供精确控制和靶向作用的药物递送系统。是由于FA对叶酸受体的亲和力高。最后，研究了阿霉素介导的视网膜母细胞瘤细胞系（Y-79）凋亡的机制，这表明线粒体途径被激活，FA偶联的DOX-CNP最有效，并导致细胞色素c的释放增强。下游胱天蛋白酶的活化以协助细胞凋亡。因此，以DOX为模型药物，证明了以FA为靶标的NP具有可持续，可控制和靶向的抗癌药物递送，这可以为治疗成视网膜细胞瘤提供精确控制和靶向作用的药物递送系统。是由于FA对叶酸受体的亲和力高。最后，研究了阿霉素介导的视网膜母细胞瘤细胞系（Y-79）凋亡的机制，这表明线粒体途径被激活，FA偶联的DOX-CNP最有效，并导致细胞色素c的释放增强。下游胱天蛋白酶的活化以协助细胞凋亡。因此，以DOX为模型药物，证明了以FA为靶标的NP具有可持续，可控制和靶向的抗癌药物递送，这可以为治疗成视网膜细胞瘤提供精确控制和靶向作用的药物递送系统。研究了阿霉素介导的视网膜母细胞瘤细胞系（Y-79）凋亡的机制，这表明线粒体途径被激活，FA偶联的DOX-CNP最有效，并导致细胞色素c的释放增强以及激活下游胱天蛋白酶有助于细胞凋亡。因此，以DOX为模型药物，证明了以FA为靶标的NP具有可持续，可控制和靶向的抗癌药物递送，这可以为治疗成视网膜细胞瘤提供精确控制和靶向作用的药物递送系统。研究了阿霉素介导的视网膜母细胞瘤细胞系（Y-79）凋亡的机制，这表明线粒体途径被激活，FA偶联的DOX-CNP最有效，并导致细胞色素c的释放增强以及激活下游胱天蛋白酶有助于细胞凋亡。因此，以DOX为模型药物，证明了以FA为靶标的NP具有可持续，可控和靶向的抗癌药物递送，这可以为治疗成视网膜细胞瘤提供精确控制和靶向作用的药物递送系统。