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
ABSTRACT Prostate cancer, the second leading cause of cancer‐related deaths, has driven research into drug delivery systems to overcome the limitations of conventional chemotherapy. Curcumin, a phenolic phytochemical from Curcuma longa , shows antioxidant, anti‐mutagenic, anti‐proliferative, anti‐inflammatory, and anticancer properties. However, its low solubility and bioavailability limit its use, leading to the development of encapsulated formulations to enhance its efficacy. Carrier‐based curcumin formulations have emerged as a promising perspective for cancer treatment. Here, we aimed to assess the in vitro anticancer activity of soy lecithin‐encapsulated curcumin ( SLC CUR) and the safety and efficacy of its intracellular uptake against prostate cancer. To this end, the intracellular uptake and cytotoxic activity of SLC CUR versus free curcumin ( F CUR) were analyzed in androgen‐sensitive 22Rv1 and LNCaP prostate cancer cells along with normal prostate epithelial cells PNT1A. Cellular uptake of SLC CUR was 15‐fold higher than F CUR, showing a greater dose‐dependent cytotoxic effect on 22Rv1 and LNCaP cells, while only a cytostatic effect was observed for PNT1A cells. In a nude mice 22Rv1 xenograft model, administration of SLC CUR resulted in a tenfold greater reduction in tumor size compared to F CUR, suggesting that the anticancer activity of curcumin is significantly improved when encapsulated in soy lecithin‐based carriers.
Abstract In this study, prostate cancer-targeted, drug-loaded PEtOx nanogel was prepared by the combination of living/cationic ring-opening polymerization and alkyne-azide cycloaddition “click” chemistry. A fluorescence probe was also conjugated with nanogel to track drug delivery. Nanogel formation was confirmed by 1H-NMR and FT-IR spectroscopies while SEM and DLS analyses showed uniform spherical nanogels and the particle size of nanogels could be controlled at 100-250 nm with relatively narrow size distributions. The physical stability of nanogels has been examined at pH 7.4 and %1-5 fetal bovine serum and intravenously administered nanogel formulations could remain in the bloodstream without much physical change until they reach the target site. The biocompatibility of the nanogels was evaluated using MTT cytotoxicity assays. The results showed that cytotoxicity was dose-dependent and drug-loaded nanogels against cancer cells in vitro were much higher than that of the drug-free nanogel. The targeting efficiency was examined with peptide conjugated and peptide-free nanogel. Intracellular uptake of peptide 563 conjugated nanogel by tumor cells was 60-fold higher than that of nanogel without peptide. Our findings suggest that prepared nanogel exhibits great potential to be used in a variety of drug delivery applications due to non-toxic, and enhanced intracellular uptake into the tumor region.
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