Abstract
Background. Nanotechnology addresses the challenge of targeted drug and nucleic acid delivery to cancer cells through the design of intelligent carriers. This study was conducted to design a smart nanocarrier based on PCL/Chitosan/PEG functionalized with hyaluronic acid (HA) for the delivery of siRNA to breast cancer cells (MCF-7).
Methods. The physicochemical properties of the synthesized nanoparticles were analyzed using 1H-NMR and TGA. Zeta potential and nanoparticle size were assessed using dynamic light scattering (DLS), confirming successful synthesis.
Results. DLS analysis revealed that after loading siRNA-FAM, the size of PCPH nanoparticles increased from 201±7 nm to 294±9 nm, and that of PEI nanoparticles from 186±11 nm to 220±6 nm. Meanwhile, siRNA loading reduced the zeta potential of PCPH nanoparticles from +1.72±0.52 mV to -2.5±0.50 mV. The results showed that at neutral pH, PEI/siRNA-FAM exhibited significantly higher release than PCPH after 480 minutes, whereas in an acidic environment, both nanoparticles released siRNA-FAM at a similar rate. Cytotoxicity assessment indicated that PCPH nanoparticles carrying siRNA had significant inhibitory effects on the growth of MCF-7 cells. The results of gel electrophoresis confirmed that PCPH nanoparticles effectively interacted electrostatically with siRNA-FAM, neutralizing its negative charge and halting its migration in the gel.
Conclusion. PCL-Chitosan-PEG-HA nanoparticles serve as a biocompatible and targeted system for siRNA delivery to cancer cells, demonstrating high efficiency in targeted gene therapy.
Practical Implications. The findings of this study represent a significant step toward more personalized and effective cancer treatments using nanotechnology.