Design and Invitro Characterization of Green Synthesized Magnetic Nanoparticles Conjugated with Multitargeted Poly Lactic Acid Copolymers for Co-delivery of siRNA and Paclitaxel

Abstract

Background: The self-assembling of various amphipathic copolymers is a simple method that allows the preparation of complex nanoparticles with several useful properties. In the present study, the polylactic acid-polyethylene glycol-folate (PLA-PEG-FA) (PPF), PLA-PEG-T7 peptide (PPT) and PLA-Chitosan-Spermine (PCS) copolymers were synthesized separately. Methods: These copolymers combined with Fe3O4 magnetic core and loaded with paclitaxel (PTX)/siRNA-FAM to form magnetic PCS/PPF/PPT/PTX/siRNA micelles (MPCSFT/PTX/siRNA) and were characterized using physicochemical and biological analysis. Results: The results revealed that the MPCSPFT/PTX/siRNA had spherical morphology with particle size and zeta potential about 197 nm and -7.8 mV, respectively. Release assay was determined under neutral (pH=7.4) and acidic pH (pH=6) conditions to simulate PTX and siRNA release profile from MPCSPFT/PTX/siRNA micelles in normal and cancerous tissues. The ability of MPCSPFT for co-delivery of PTX and siRNA into MCF-7 cells was determined by MTT and flow cytometry tests, respectively. The results revealed that the release rate of siRNA and PTX from MPCSPFT/PTX/siRNA nanoparticles under an acidic environment (pH=6) was significantly higher than that of their release rate in a neutral medium (pH=7.4). Conclusion: Conjugation of both folic acid and T7-peptide on the surface of micelles compared to separate conjugation of one of these ligands, increased the efficiency of drug and siRNA delivery to breast cancer cells.