Valiollah Mirkhani, Ph.D. ,

This study introduces a novel carrier system based on thiolated sodium alginate (TSA), a biopolymer used for drug loading. Sodium alginate was modified with 1,2–ethane dithiol to cross-link the polymer and introduce thiol functional groups. The resulting TSA matrix was used to immobilize gold nanoparticles (AuNPs) and 6-mercaptopurine (6-MP). Two types of nanocarriers, 6-MP–Auₙₚ@TSA and 6-MP@TSA, were prepared and characterized using Fourier-transform infrared spectroscopy (FT-IR), surface-enhanced Raman spectroscopy (SERS), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). TEM analysis revealed that the synthesized fine Au nanoparticles have an average diameter of approximately 2.4 nm. These platforms were evaluated and compared in terms of drug loading capacity and release behavior. The Auₙₚ@TSA carrier demonstrated a higher drug-loading capacity and superior controlled-release characteristics. The nanocomposites achieved drug loading efficiencies of 93% and 74% for Auₙₚ@TSA and TSA, respectively, and exhibited pH-sensitive release profiles for 6-MP. Under acidic conditions (low pH), the drug-loaded carriers exhibited reduced swelling, with swelling degrees of approximately 13–20% for samples, likely due to hydrogen bonding that limited water penetration. Cytotoxicity assessments were conducted on the human breast cancer cell line MCF-7 over a 50-h period. Notably, both carriers showed minimal cytotoxic effects on healthy and cancerous cells at low concentrations. Free 6-MP induced approximately 30% reduction in cancer cell viability at 50 µg/mL. In comparison, the 6-MP–Auₙₚ@TSA and 6-MP@TSA carriers reduced cell viability by 55% and 48%, respectively, after 50 h. Furthermore, 6-MP@TSA and 6-MP–AuNP@TSA showed enhanced cytotoxicity against MCF7 cells, with lower IC₅₀ values (70 μM and 26 μM, respectively) compared to free 6-MP. These results highlight the potential of TSA-based biocarriers as biocompatible and degradable platforms for targeted drug delivery, particularly in anticancer applications. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.