Breast cancer is the second leading cause of mortality in women worldwide. Chemotherapeutic drugs like docetaxel (DTX) remain key molecules in cancer management. Silibinin (SLB) is an effective agent causing apoptosis and autophagy resulting in cancer cell death. Recently, ligand-anchored targeted nanocarrier-based drug delivery has achieved substantial improvement in cancer therapy. In the present study, chondroitin sulfate (CS) was used as a ligand to target CD44 receptors overexpressed in breast cancer cells. Herein, CS-coated chitosan–lecithin nanoparticles (CS-DTX-SLB-LCNPs) were developed for co-delivery of DTX and SLB. The CS-DTX-SLB-LCNP resulted in a particle size of 208.33 ± 2.20 nm with an entrapment efficiency of 83.81% for DTX and 92.96% for SLB. Further, the dialysis release study showed sustained release behavior, and a hemocompatible nature which was proved by the hemolysis study. The cell cytotoxicity in MDA-MB-231 cells revealed considerably higher cell killing with CS-DTX-SLB-LCNP compared to free drugs. The cell uptake studies showed a 1.97-fold and 2.45-fold rise in fluorescence intensity from C6-LCNP and CS-C6-LCNP, respectively, as compared to free C6. CS-DTX-SLB-LCNP caused a sharp rise in the ROS level and resulted in mitochondrial membrane depolarization, which induced apoptosis and cell death. An in vivo efficacy study in Balb/c mice demonstrated 2.24-fold and 2-fold reduction in tumor volume after CS-DTX-SLB-LCNP treatment as compared to free DTX and free SLB groups. In conclusion, CS-DTX-SLB-LCNPs showed encouraging prospects in increasing cellular uptake and targeting specificity to treat breast cancer.
Aalhate et al. (Mon,) studied this question.
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