Iranian Journal of

Introduction: Nanotechnology addresses the challenge of targeted delivery of drugs and nucleic acids to cancer cells by designing smart delivery systems. This approach enables improved precision and efficiency in the delivery of therapeutic agents. This study focuses on the design and evaluation of a folic acid (FA)-functionalized, PLA/Chitosan/PEG-based multifunctional nanocarrier with tumor-targeting capability and synergistic co-delivery of paclitaxel (PTX) and siRNA to breast cancer cells (MCF-7), aiming to enhance selective uptake and therapeutic efficiency compared to conventional delivery systems.
Methods: PCPF nanoparticles were synthesized and co-loaded with PTX and Survivin-targeting siRNA. FTIR and DLS characterized physicochemical properties. Cargo release was evaluated at different pH values, while cytotoxicity and apoptosis were assessed in MCF-7 and MCF-10A cells using MTT and Annexin V/PI assays, respectively.
Results: FTIR confirmed successful PCPF nanoparticle synthesis. Particle size increased from 162 ± 6 nm to 256 ± 11 nm after PTX/siRNA loading, while zeta potential remained mainly negative. Nanocapsules exhibited pH-responsive sustained release, with greater cargo release at pH 5.0. Cytotoxicity studies demonstrated enhanced selectivity for MCF-7 cells, with PCPF/PTX/siRNA inducing the highest apoptosis, whereas free PTX caused the greatest necrosis.
Conclusion: Folic acid-targeted PCPF nanoparticles enhanced PTX/siRNA co-delivery, promoting selective cytotoxicity, apoptosis, and improved anticancer efficacy.