Abstract：
Active targeting can enhance precision and efficacy of drug delivery systems (DDS) against cancers. Riboflavin (RF) is a promising ligand for active targeting due to its biocompatibility and high riboflavin-receptor expression in cancers. In this study, RF-targeted 4-arm polyethylene glycol (PEG) stars conjugated with Paclitaxel (PTX), named PEG PTX RF, were evaluated as a targeted DDS. In vitro, PEG PTX RF exhibited higher toxicity against tumor cells compared to the non-targeted counterpart (PEG PTX), while free PTX displayed the highest acute toxicity. In vivo, all treatments were similarly effective, but PEG PTX RF-treated tumors showed fewer proliferating cells, pointing to sustained therapy effects. Moreover, PTX-treated animals\' body and liver weights were significantly reduced, whereas both remained stable in PEG PTX and PEG PTX RF-treated animals. Overall, our targeted and non-targeted DDS reduced PTX\'s adverse effects, with RF targeting promoted drug uptake in cancer cells for sustained therapeutic effect.
摘要：
主动靶向可以增强药物递送系统(DDS)针对癌症的精确度和功效。核黄素（RF）由于其生物相容性和在癌症中的高核黄素受体表达，是一种有前途的活性靶向配体。在这项研究中,射频靶向四臂聚乙二醇（PEG）星与紫杉醇（PTX）缀合，名为PEGPTXRF，被评价为靶向DDS。体外，与非靶向对应物（PEGPTX）相比，PEGPTXRF对肿瘤细胞表现出更高的毒性，而游离PTX的急性毒性最高。在体内,所有治疗方法都同样有效，但PEGPTX射频治疗的肿瘤显示增殖细胞较少，指向持续的治疗效果。此外，经PTX处理的动物体重和肝脏重量显著减少，而两者在PEGPTX和PEGPTXRF治疗的动物中保持稳定。总的来说,我们的靶向和非靶向DDS减少了PTX的不良反应，与RF靶向促进药物在癌细胞中的摄取，以获得持续的治疗效果。
