Darguzyte, MilitaMilitaDarguzyteRama, ElenaElenaRamaRix, AnneAnneRixBaier, JasminJasminBaierHermann, JulianeJulianeHermannRezvantalab, SimaSimaRezvantalabKhedri, MohammadMohammadKhedriJankowski, Joachim T.Joachim T.JankowskiKießling, FabianFabianKießling2024-08-292024-08-292024https://publica.fraunhofer.de/handle/publica/47427310.1016/j.nano.2024.1027512-s2.0-8519223225538705222Active 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.enopen accessActive targetingDrug delivery systemsMolecular simulationPaclitaxelPEGRiboflavinjournal article