ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

A novel glutathione-sensitive and folic acid-modified nanocarrier for tumor-targeted drug delivery

Farzaneh Sadrykia, Peyman Najafi Moghadam, and Hamed Hamishehkar

Department of Organic Chemistry, Faculty of Chemistry, Urmia University, Urmia, Iran

E-mail: p_najafi27@yahoo.com

Received: 8 April 2024  Accepted: 25 May 2026

Abstract:

Nowadays, scientists are trying to design a developed nanocarrier for delivering drugs specifically to cancerous cells. This study aimed to design the poly (acrylamide-maleic anhydride-POSS)/(FA & TPGS) nanocarrier (P(AAm-MA-POSS)/(FA & TPGS) NC) as a GSH-sensitive and folic acid (FA)-modified targeted drug delivery system. For this purpose, the P(AAm-MA-POSS)/(FA & TPGS) copolymer was synthesized via free radical polymerization of AAm, MA, and POSS-glycidyl methacrylate (POSS-GMA) monomers, followed by chemical grafting of FA-NH₂ and TPGS-SS-NH₂. Finally, the synthesized copolymer was self-assembled into the P(AAm-MA-POSS)/(FA & TPGS) nanocarrier with a hydrophobic POSS-based core surrounded by the hydrophilic TPGS and FA moieties. Sorafenib tosylate (ST) drug was encapsulated during the nanocarrier preparation. The TEM and DLS results confirmed the successful preparation of a self-assembled nanocarrier with around 100 nm diameter. The prepared nanocarrier exhibited enhanced cellular uptake through FA receptor-mediated endocytosis and GSH-sensitive drug release owing to the disulfide bond cleavage in the presence of reductive GSH. The efficiency of prepared ST-loaded nanocarrier against MCF-7 cancer cells was verified by MTT, and decreased amounts of the IC₅₀ for this ST-loaded nanocarrier compared to pure ST exhibited higher cytotoxicity of the drug-loaded nanocarrier. Thus, the developed targeted nanocarrier can be a suitable choice for inhibiting cancer cells.

Keywords: Targeted drug delivery; Self-assembled nanocarrier; Glutathione-sensitive; Folic acid

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-05117-5

Chemical Papers 80 (10) 12073–12091 (2026)