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

Author:

Gülyüz Sevgi1ORCID,Sessevmez Melike2ORCID,Ukuser Gokcen1ORCID,Khalily Melek Parlak3ORCID,Tiryaki Selen4ORCID,Sipahioglu Tarik4ORCID,Birgül Kaan5ORCID,Ömeroğlu İpek6,Özçubukçu Salih7ORCID,Telci Dilek4ORCID,Küçükgüzel Ş. Güniz8ORCID,Durmuş Mahmut6ORCID,Cevher Erdal2ORCID,Yılmaz Özgür1ORCID

Affiliation:

1. Material Technologies Marmara Research Center TUBITAK Gebze Kocaeli 41470 Turkey

2. Department of Pharmaceutical Technology Istanbul University Istanbul 34116 Turkey

3. Department of Basic Science and Health Cannabis Research Institute Yozgat Bozok University Yozgat 66100 Turkey

4. Department of Genetics and Bioengineering Yeditepe University Istanbul 34755 Turkey

5. Department of Pharmaceutical Chemistry School of Pharmacy Bahçeşehir University Beşiktaş Istanbul 34353 Turkey

6. Department of Chemistry, Gebze Technical University Gebze Kocaeli 41400 Turkey

7. Department of Chemistry Middle East Technical University Ankara 06800 Turkey

8. Department of Pharmaceutical Chemistry Fenerbahçe University Ataşehir Istanbul 34758 Turkey

Abstract

AbstractThis 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 1H‐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.

Publisher

Wiley

Subject

Materials Chemistry,Polymers and Plastics,Biomaterials,Bioengineering,Biotechnology

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