A Novel PEtOx-Based Nanogel Targeting Prostate Cancer Cells for Drug Delivery

Macromol Biosci. 2024 Mar;24(3):e2300324. doi: 10.1002/mabi.202300324. Epub 2023 Oct 22.

Abstract

This study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx nanogel) is created using hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) through a combination of living/cationic ring-opening polymerization (CROP) and alkyne-azide cycloaddition (CuAAC) "click" chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through 1 H-NMR, and FT-IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose-dependent cytotoxicity. Drug-loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug-free nanogels. Targeting efficiency is examined using both peptide-conjugated and peptide-free nanogels, with the intracellular uptake of peptide 563-conjugated nanogels by tumor cells being 60-fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non-toxicity, and enhanced intracellular uptake in the tumor region.

Keywords: CuAAC click chemistry; cytotoxicity; nanogels; peptide; prostate cancer; star poly(2-ethyl-2-oxazoline); targeted drug delivery.

MeSH terms

  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Humans
  • Male
  • Nanogels
  • Peptides / pharmacology
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine*
  • Prostatic Neoplasms* / drug therapy
  • Spectroscopy, Fourier Transform Infrared

Substances

  • polyethylene glycol polyethyleneimine nanogel
  • Nanogels
  • Polyethylene Glycols
  • Peptides
  • Drug Carriers
  • Polyethyleneimine