This study aimed to improve the magnetofection of MG-63 osteoblasts by integrating the use of a novel uniform magnetic field with low molecular weight polyethylenimine modified superparamagnetic iron oxide nanoparticles (PEI-SPIO-NPs). The excellent characteristics of PEI-SPIO-NPs such as size, zeta potential, the pDNA binding and protective ability were determined to be suitable for gene delivery. The novel uniform magnetic field enabled polyethylenimine-modified superparamagnetic iron oxide nanoparticles/pDNA complexes (PEI-SPIO-NPs/pDNA complexes) to rapidly and uniformly distribute on the surface of MG-63 cells, averting local transfection and decreasing disruption of the membrane caused by the centralization of positively charged PEI-SPIO-NPs, thereby increasing the effective coverage of magnetic gene carriers during transfection, and improving magnetofection efficiency. This innovative uniform magnetic field can be used to determine the optimal amount between PEI-SPIO-NPs and pDNA, as well as screen for the optimal formulation design of magnetic gene carrier under the homogenous conditions. Most importantly, the novel uniform magnetic field facilitates the transfection of PEI-SPIO-NPs/pDNA into osteoblasts, thereby providing a novel approach for the targeted delivery of therapeutic genes to osteosarcoma tissues as well as a reference for the treatment of other tumors.
Ao Hu,Xiaobing Chen,Qunjie Bi,Yang Xiang,Rongrong Jin,Hua Ai,Yu Nie
Polarization regulation of tumor-association macrophages (TAMs) is a promising treatment method for tumors, but aiming at TAMs alone shows unsatisfactory therapeutic efficiency. Therefore, we designed a parallel and cascade control system for both macrophage polarization and tumor cell inhibition. The system is composed of cationic lipopeptides with an arginine-rich periphery (RLS) and anionic magnetic nanoparticles (MNPs) for fleet transfection of miR-125b. Based on the highly efficient magnetofection, miR-125b successfully shows a parallel effect on both M1, promoting polarization by targeting interferon regulatory factor 4 (IRF4) in macrophages, and tumor cell inhibition, by targeting ETS proto-oncogene 1 and cyclin- J. The cascading effect on M1-associated genes is upregulated by up to two orders of magnitude, while M2-associated genes are downregulated. Meanwhile, MNPs also have an effect on the TAM polarization and 4T1 tumor cell inhibition via inflammatory related gene expression and Fenton reaction. Further mimicking the co-culture of RAW264.7 and 4T1 cells in vitro confirmed the synergistic therapy effect. In the treatment of orthotopic breast cancer in mice, considerable M1 macrophage polarization was observed in the RM125b treated group, showing distinct tumor-suppressive effects, with a tumor weight reduction of 60% and tumor metastasis suppression of 50%.
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