Bioconjugated clicked chitosan/alginate nanocarriers with trastuzumab: Unlocking curcumin's potential in targeting breast cancer

Curcumin (Cur) has shown potential anticancer effects against various cancers, including colorectal and breast cancers. The aim of this study was to develop nanocarriers (NCs) bioconjugated with trastuzumab (Tras) using click reactions. Chitosan-maleimide (CHI-Mal) and thiolated alginate (SH-ALG) were synthesized to prepare CS-Mal/SH-ALG NCs, which were then conjugated with Tras as a receptor-targeting ligand via click chemistry. The characteristics of the NCs, including Cur loading and release profiles, were examined. Biocompatibility, anticancer effects, targetability, and cell death analysis were conducted on HER2-positive breast cancer cell line (SK-BR-3). The developed NCs exhibited a nano-scaled size, relatively spherical shape, and positive surface charge. The 7-day release of Cur from the Cur-loaded CHI-Mal/SH-ALG NCs (Cur-NCs) was significantly higher in the cancer environment (pH 5.5; 98%) compared to body fluid (pH 7.4; 57%). Tras-conjugated Cur-NCs (Tras-Cur-NCs) demonstrated superior anticancer effects, receptor-targeting efficiency, and cellular uptake compared to free Cur and non-targeted Cur-NCs. Additionally, Tras-Cur-NCs enhanced apoptotic cell death, indicating a non-inflammatory cell death with strong anticancer effect against HER2-positive SK-BR-3 cells. The spontaneous click reaction successfully formed pH-responsive Tras-conjugated NCs for targeted Cur delivery to HER2-positive breast cancer cells.