Docetaxel-loaded redox-sensitive nanoparticles self-assembling from poly(caprolactone) conjugates with disulfide-linked poly(ethylene glycol)

J Biomater Sci Polym Ed. 2022 Dec;33(17):2185-2201. doi: 10.1080/09205063.2022.2099664. Epub 2022 Jul 19.

Abstract

In this study, novel redox-sensitive nanoparticles (NPs) were fabricated from the poly(caprolactone) conjugates with disulfide-linked poly(ethylene glycol) (DDMAT- mPEG-S-S-PCL, DPSP). The DPSP polymer was synthesized by ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtaining of the DPSP polymer was confirmed by the 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR) spectra. The DPSP NPs were fabricated with the solvent-evaporation method. Docetaxel (DTX) was employed as a model drug and encapsulated into the DPSP NPs. The in vitro anti-tumor activity of the DTX-loaded DPSP NPs and free DTX against the breast cancer cells (4T1) were evaluated by MTT assay. The cargo-free DPSP NPs were in circular shapes with an average diameter of 107.8 ± 0.4 nm. These NPs displayed redox-responsive behavior in the presence of glutathione. Animal experiments indicated that the DPSP NPs showed excellent blood compatibility and good bio-security. Cell tests suggested that the DPSP NPs could be taken in by 4T1 cells, smoothly, which improved the anti-tumor activity of free DTX.

Keywords: Docetaxel; anti-tumor activity; bio-security; glutathione; redox-sensitive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Disulfides
  • Docetaxel
  • Drug Carriers / chemistry
  • Nanoparticles* / chemistry
  • Oxidation-Reduction
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry

Substances

  • polycaprolactone
  • Docetaxel
  • Disulfides
  • Drug Carriers
  • Antineoplastic Agents
  • Polyesters
  • methoxy poly(ethylene glycol-co-epsilon-caprolactone)
  • Polyethylene Glycols
  • caprolactone
  • Polymers