Multifunctional magnetic nanocapsules for dual delivery of siRNA and chemotherapy to MCF-7 cells (Breast cancer cells)

Abstract

The targeted delivery of nucleic acids and drugs via nanoparticles to damaged cells remains a significant challenge in cancer treatment. This study focused on the bipolar copolymer Fe₃O₄/chitosan/polycaprolactone (PCL)/polyethylene glycol (PEG)-hyaluronic acid (HA) nanocapsules designed to enhance drug delivery to CD₄₄ receptor-expressing MCF-7 cancer cells. These nanoparticles integrate iron oxide, hydrophilic PEG, biodegradable PCL, cationic chitosan, and hyaluronic acid. The physicochemical properties of the nanoparticles were investigated and confirmed via Fourier transform infrared (FTIR) spectroscopy and differential thermogravimetric (DTG) analysis. After paclitaxel (PTX) and siRNA-FAM loading, the zeta potential, dynamic light scattering (DLS), and scanning electron microscopy (SEM) confirmed the successful synthesis and appropriate structural properties of the nanocapsules. The nanocapsules were measured at approximately 230 nm with a zeta potential of - 2.5 mV. Release studies at pH 5 and 7.4 demonstrated that a lower pH significantly increased the release rates of PTX and siRNA-FAM. Electrophoretic analysis indicated that the nanocapsule coating (controlled-release nanoprotective coating) protected these agents from plasma degradation. An evaluation of the magnetic properties via a vibrating sample magnetometer (VSM) revealed that the iron oxide nanoparticles exhibited desirable magnetic characteristics, with values decreasing from 42.5 to 16.8 emu/g upon encapsulation. Cytotoxicity assessments via the MTT assay indicated the low toxicity (IC₅₀ = 492.7 μg/mL) of the nanocapsules to the MCF-7 cell line. Flow cytometry revealed effective targeted gene transfer, with significant pre- and post-apoptosis rates (18.14% and 15.65%, respectively) for the Fe₃O₄/chitosan/PCL/PEG-HA/PTX treatment. The agarose gel and fluorescence microscopy results confirmed the superior gene transfer efficiency of the Fe₃O₄/chitosan/PCL/PEG-HA/siRNA-FAM nanocapsules compared with the controls, which was attributed to their stability and the presence of hyaluronic acid groups. This study presents the first application of these nanocapsules for gene and drug delivery.

Keywords: Apoptosis; Drug delivery; Magnetic nanoparticles; Nanocapsules; Targeting; Zeta potential.