Folic acid-functionalized Exemestane-loaded chitosan nanoparticles: Synthesis, characterization and enhanced cytotoxicity against MCF-7 breast cancer cells

The development of biocompatible and potent nanocarriers is demanded for improved therapeutics and reduced dosage of anticancer drug for breast cancer treatment. In this study, ionic gelation method was used to synthesize chitosan nanoparticles subsequently loaded with Exemestane and conjugated with folic acid (EXM-CS-FA). This nanoconjugate was characterized through UV–Vis spectroscopy, FT-IR, zeta-sizer, SEM-EDX, and XRD and then subjected to drug formulation and characterization through encapsulation efficiency assay, drug release assay, biocompatibility analysis through hemolysis assay, MTT assay and DNA damage assay, and antioxidant potential analysis through DPPH assay. The study findings have shown UV–Vis characteristic peaks at 209 nm, 250 nm and 285 nm confirming the presence of chitosan NPs, Exemestane, and folic acid in nanoconjugate with hydrodynamic diameter 540 nm through zeta-sizer. FT-IR spectrum of EXM-CS-FA showed various broad and sharp peaks at 3797, 3605, 3309, 3138, 2674, 1572, 1062, and 877 cm −1 while SEM-EDX profile showed smooth morphology with strong interactions of drug and NPs. The XRD spectrum showed distinct peaks at 2θ of 12°, 18°, 23°, and 26°, which defined plane, indexed at (020), (110), (120,200). The drug formulation showed high encapsulation efficiency i.e. 73.0 ± 1.5% of chitosan NPs with pH responsive drug releasing potential while hemolysis assay revealed strong biocompatible nature of EXM-CS-FA with reduced IC 50 value 41.67 μg/mL indicating its excellent cytotoxic nature for cancer cells and negligible DNA damage in human body. The DPPH assay revealed dose-dependent antioxidant potential of nanoconjugate and achieved maximum i.e. 67 ± 0.8% at 400 μg/mL. Overall, these results highlighted the importance of chitosan NPs as a promising nanocarrier with enhanced activity for breast cancer therapy, combining its biocompatibility, non-genotoxicity for healthy cells with enhanced cytotoxicity for tumor cells. However, further safety assessments, preclinical evaluation and in vivo studies required for clinical applicability.