Low-Molecular-Weight Poly(ethylenimine) Nanogels Loaded with Ultrasmall Iron Oxide Nanoparticles for T1-Weighted MR Imaging-Guided Gene Therapy of Sarcoma.

Abstract

Cancer metastasis is still a major obstacle in clinical cancer therapy and a paramount cause of cancer deaths. Designing multifunctional nanoplatforms with an enhanced diagnostic sensitivity and anti-metastasis efficiency against tumors represents a major trend in current cancer management. Herein, we report the preparation of low-molecular-weight poly(ethylenimine) (PEI)-poly(ethylene glycol) (PEG) nanogels (NGs) loaded with transforming growth factor-β1 (TGF-β1) siRNA and ultrasmall iron oxide nanoparticles (Fe3O4 NPs) for gene therapy and T1-weighted magnetic resonance (MR) imaging of tumors and tumor metastasis in a mouse sarcoma model. In this work, ultrasmall Fe3O4 NPs stabilized by sodium citrate were first prepared and then mixed with PEI (800 Da) and PEG (400 Da)-diacrylate as a cross-linker to form Fe3O4/PEI-PEG NGs with an average size of 76.3 nm via an inverse microemulsion method. The developed hybrid NGs display good cytocompatibility and enhanced MR imaging performance (r1 relaxivity = 1.0346 mM-1 s-1). The Fe3O4/PEI-PEG NGs can be further used to compact TGF-β1 siRNA through electrostatic interaction and efficiently deliver siRNA to cancer cells and a tumor model to silence the TGF-β1 gene, which inhibits the growth and invasion of cancer cell in vitro significantly, as well as the growth of a subcutaneous sarcoma tumor model and lung metastasis in vivo. The designed hybrid NG-ultrasmall iron oxide NPs may be extended for the delivery of other drugs or genes for theranostics of different biological systems.