pH-bioresponsive poly(ε-caprolactone)-based polymersome for effective drug delivery in cancer and protein glycoxidation prevention

Arch Biochem Biophys. 2020 Nov 30:695:108643. doi: 10.1016/j.abb.2020.108643. Epub 2020 Oct 22.

Abstract

Artificial nanostructures using polymers to produce polymeric vesicles are inspired by the many intricate structures found in living organisms. Polymersomes are a class of self-assembled vesicles known for their great stability and application in drug delivery. They can be tuned according to their intended use by changing their components and introducing activable block copolymers that transform these polymersomes into smart nanocarriers. In this study, we propose the synthesis of a poly (ethylene oxide)-poly (ε-caprolactone)-based polymersome (PEO-PCL) loaded with GSH as a pH-responsive drug delivery molecule for cancer and protein alteration inhibition. Initially, the nanocarrier was synthesized and characterized by DLS, TEM/SEM microscopy as well as gel permeation chromatography (GPC) and 1H NMR. Their CMC formation, encapsulation efficiency, and pH responsiveness were analyzed. In addition, empty and GSH-loaded PEO-PCL polymersomes were tested for their toxicity and therapeutic effect on normal and cancer cells via an MTT test. Subsequently, protein alteration models (aggregation, glycation, and oxidation) were performed in vitro where the polymersomes were tested. Results showed that other than being non-toxic and able to highly encapsulate and release the GSH in response to acidic conditions, the nanocomposites do not hinder its content's ameliorative effects on cancer cells and protein alterations. This infers that polymeric nanocarriers can be a base for future smart biomedicine applications and theranostics.

Keywords: Caprolactone; GSH; Polymersome; Protein alteration; Smart drug delivery; pH-responsive.

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Drug Carriers* / pharmacology
  • Glutathione* / chemistry
  • Glutathione* / pharmacokinetics
  • Glutathione* / pharmacology
  • Glycosylation / drug effects
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Neoplasm Proteins / metabolism*
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Polyesters* / chemistry
  • Polyesters* / pharmacokinetics
  • Polyesters* / pharmacology
  • Vero Cells

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Neoplasm Proteins
  • Polyesters
  • polycaprolactone
  • Glutathione