Surface modified magnetic nanoparticles for immuno-gene therapy of murine mammary adenocarcinoma

Abstract

Cancer immuno-gene therapy is an introduction of nucleic acids encoding immunostimulatory proteins, such as cytokine interleukin 12 (IL-12), into somatic cells to stimulate an immune response against a tumor. Various methods can be used for the introduction of nucleic acids into cells; magnetofection involves binding of nucleic acids to magnetic nanoparticles with subsequent exposure to an external magnetic field. Here we show that surface modified superparamagnetic iron oxide nanoparticles (SPIONs) with a combination of polyacrylic acid (PAA) and polyethylenimine (PEI) (SPIONs-PAA-PEI) proved to be safe and effective for magnetofection of cells and tumors in mice. Magnetofection of cells with plasmid DNA encoding reporter gene using SPIONs-PAA-PEI was superior in transfection efficiency to commercially available SPIONs. Magnetofection of murine mammary adenocarcinoma with plasmid DNA encoding IL-12 using SPIONs-PAA-PEI resulted in significant antitumor effect and could be further refined for cancer immuno-gene therapy.

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…[633] In the matter of delivering nucleic acids, including siRNA and genes, MNPs have been shown promising for a practical magnetofection through exploiting nanoassemblies integrated with cationic coatings to nucleic acids. [634] This approach has especially enhanced the efficiency of siRNA transfection under a permanent magnet in both in vitro and/or in vivo experiments against breast [635] and prostate [636] cancers. In addition, utilizing MNPs coated with PET has shown a great potential for complexation of plasmid DNA on the surface of nanoparticles for delivering DNA vaccine.…”

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

“…[69][70][71][72][73] By this means, siRNA, electrostatically associated with magnetic nanocarriers could be transferred directly into cancers via AMF therapy. Such magnetofection has improved effectiveness in the transfection of nucleic acids in vitro and in vivo.…”

In vitro assessment of potential bladder papillary neoplasm treatment with functionalized polyethyleneimine coated magnetic nanoparticles

“…PEI is a cationic polymer with one of the highest cationic charge-density potentials, 19 that is mostly used as a transfection agent. 20,21 PEI has been already successfully applied as a delivery vehicle on bladder cancer models 22,23 and researchers have also used PEI in a clinical study for the treatment of bladder cancer (NCT00595088). However, cationic properties of PEI are also responsible for its toxicity [24][25][26][27][28] either through direct membrane damage (i.e.…”

“…20,31,34 PEI NPs were additionally functionalized with L-glutathione reduced (GSH; Sigma-Aldrich, St. Luis, Missouri, USA) at 0.25 to 1 mass ratio (PEI_GSH NPs), or with bovine serum albumin (BSA; Sigma-Aldrich) at 0.5 to 1 mass ratio (PEI_BSA NPs) immediately prior to use. NPs were dialyzed against distilled water and sterilized by filtration.…”