Riboflavin-targeted polymers improve tolerance of paclitaxel while maintaining therapeutic efficacy

Milita Darguzyte; Elena Rama; Anne Rix; Jasmin Baier; Juliane Hermann; Sima Rezvantalab; Mohammad Khedri; Joachim Jankowski; Fabian Kiessling

doi:10.1016/j.nano.2024.102751

Riboflavin-targeted polymers improve tolerance of paclitaxel while maintaining therapeutic efficacy

Nanomedicine. 2024 May 3:58:102751. doi: 10.1016/j.nano.2024.102751. Online ahead of print.

Authors

Milita Darguzyte¹, Elena Rama², Anne Rix², Jasmin Baier², Juliane Hermann³, Sima Rezvantalab⁴, Mohammad Khedri⁵, Joachim Jankowski³, Fabian Kiessling⁶

Affiliations

¹ Institute for Experimental Molecular Imaging, University Hospital Aachen, Forckenbeckstrasse 55, 52074 Aachen, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, Center for Molecular Medicine Cologne, 50931 Cologne, Germany; Institute for Translational Immune-Oncology, Cancer Research Center Cologne-Essen (CCCE), University of Cologne, 50931 Cologne, Germany.
² Institute for Experimental Molecular Imaging, University Hospital Aachen, Forckenbeckstrasse 55, 52074 Aachen, Germany.
³ Institute of Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany.
⁴ Department of Chemical Engineering, Urmia University of Technology, 57166-419, Urmia, Iran.
⁵ Computational Biology and Chemistry Group (CBCG) Universal Scientific Education and Research Network (USERN), 19839-63113 Tehran, Iran.
⁶ Institute for Experimental Molecular Imaging, University Hospital Aachen, Forckenbeckstrasse 55, 52074 Aachen, Germany; Fraunhofer MEVIS, Institute for Medical Image Computing, Forckenbeckstrasse 55, 52074 Aachen, Germany. Electronic address: fkiessling@ukaachen.de.

PMID: 38705222
DOI: 10.1016/j.nano.2024.102751

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.

Keywords: Active targeting; Drug delivery systems; Molecular simulation; PEG; Paclitaxel; Riboflavin.