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

Nanomedicine. 2024 Jun:58:102751. doi: 10.1016/j.nano.2024.102751. Epub 2024 May 3.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Paclitaxel* / chemistry
  • Paclitaxel* / pharmacology
  • Polyethylene Glycols* / chemistry
  • Polymers / chemistry
  • Riboflavin* / chemistry
  • Riboflavin* / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Paclitaxel
  • Riboflavin
  • Polyethylene Glycols
  • Polymers
  • Antineoplastic Agents, Phytogenic