Tabriz University of Medical Sciences Medical Journal of Tabriz University of Medical Sciences 2783-2031 48 3 2026 08 03 Engineering of multifunctional nanocarriers based on biopolymers for siRNA delivery, selective targeting, and enhanced biostability in MCF-7 cell lines 240 253 10.34172/mj.026.35311 EN Hashem Yaghoubi https://orcid.org/0000-0003-3449-3037 Mehran Noruzpour https://orcid.org/0009-0003-3447-0035 Journal Article 10.34172/mj.026.35311 2026 04 04 2026 05 25 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.