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

This study, focusing on nanogel-based drug delivery systems with significant potential in cancer treatment, involves the development of a specially designed nanogel that targets prostate cancer and carries drug payloads. This nanogel is created using hydrophilic poly(2-ethyl-2-oxazoline) (referred to as SGK 636/Peptide 563/PEtOx nanogel) and is prepared 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 accuracy of nanogel formation is confirmed through 1 H-NMR and FT-IR spectroscopies, while SEM, TEM and DLS analyses indicate the presence of uniform and spherical nanogels with controllable particle sizes ranging from 100 to 296 nm and narrow size distributions. The physical stability of nanogels was assessed at pH 7.4 and in the presence of 1-5% fetal bovine serum. Nanogel formulations administered intravenously remain relatively unchanged in the bloodstream until they reach the target site. The biocompatibility of nanogels was 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 was 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. Our 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. This article is protected by copyright. All rights reserved.