Magnetic albumin immuno-nanospheres as an efficient gene delivery system for a potential use in lung cancer: preparation, in vitro targeting and biological effect analysis

Abstract

Magnetic albumin immuno-nanospheres (MAINs), simultaneously loaded with super-paramagnetic iron oxide nanoparticles for targeting application and anticancer gene, plasmid-survivin/shRNA (pshRNA) and modified with anti-EGFR monoclonal antibody Cetuximab for targeting and treatment agents, were prepared for targeting lung cancer. Transmission electron microscopy images and transfection photographs, respectively, showed that magnetic nanoparticles and pshRNA were successfully encased in the albumin nanospheres. The release profiles in vitro indicated that nanospheres had an obvious effect of sustained release of pshRNA. The results of slide agglutination test and immunofluorescence analysis demonstrated that the immuno-nanospheres retained the immuno-reactivity of Cetuximab. The MAINs significantly increased adherence and uptake by GLC-82 lung cancer cells over-expressed epidermal growth factor receptor over a magnetic albumin nanospheres (MANs) control. The pshRNA-loaded MAINs formulation was more effective than equimolar doses of free Cetuximab, single magnetic targeting with pshRNA (pshRNA-loaded MANs) or single monoclonal antibody targeting with pshRNA (pshRNA-loaded AINs) in the treatment of GLC-82 lung cancer cells. Collectively, the study indicates that the novel pshRNA-loaded magnetic immuno-nanospheres represent a promising approach for magnetic and monoclonal antibody-dependent gene targeting in lung cancer therapy.

Albumin Nanostructures for Nucleic Acid Delivery in Cancer: Current Trend, Emerging Issues, and Possible Solutions

“…Albumin-based nanoparticles are emerging as suitable candidates for plasmid delivery in cancer therapy because of the high efficiency of DNA transfection into tumor cells, non-toxicity, and biodegradability imparted by albumin molecules. Albumin nanoparticles loaded with plasmids have shown anti-tumor efficacy in various cancers, including breast, pancreatic, brain, and lung [ 23 , 24 , 58 , 59 ]. For instance, BSA nanoparticles encapsulating the hMDA-7 plasmid, which encodes for the melanoma differentiation-associated gene, were used against pancreatic cancer [ 24 ].…”

“…This formulation enhances the biocompatibility of MNPs, due to the presence of albumin. Furthermore, the presence of MNPs allows for better control of the release of encapsulated genes since it can be triggered by magnetic hyperthermia, and also, the accumulation of the nanoparticles in the tumor can be enhanced through magnetic targeting [ 59 , 60 ]. In this regard, Hou and co-workers employed iron oxide SPIONs encapsulated in albumin nanospheres to deliver survivin-shRNA plasmid encoding short hairpin RNA (shRNA).…”

“…In this regard, Hou and co-workers employed iron oxide SPIONs encapsulated in albumin nanospheres to deliver survivin-shRNA plasmid encoding short hairpin RNA (shRNA). The system was precisely delivered to the tumor cells in the lung by placing a magnet close to the tumor (magnetic targeting) [ 59 ]. In another study, Zhang and co-workers evaluated the combination of the delivery of a plasmid encoding for IFNγ with radiation therapy [ 60 ].…”

Microfluidic Synthesis of Vinblastine-Loaded Multifunctional Particles for Magnetically Responsive Controlled Drug Release

“…For example, Kost et al conducted pulsatile release from polymer composites by using external magnetic fields and externally controlled insulin release from a magnetic ethylene–vinyl acetate copolymer [28]. Magnetically guidable NPs have also been used to deliver nucleic acid, enzymes, genes, DNA vaccine, siRNA, or anticancer drugs by using an external magnet for reducing multidrug resistance, avoiding drug degradation during delivery, or achieving effective silencing effects [29].…”

Study of the combined treatment of lung cancer using gene-loaded immunomagnetic albumin nanospheres in vitro and in vivo

“…We fused C225 to MANS to construct IMANS; then, we used IMANS for diagnosis or treatment. 55,56 In these studies, we have evaluated the immunoreactivity of immunonanospheres and the results showed that C225 fused to the particles maintain their ability to react with IgG antiserum. Hence, in this study, we adopted this technology to construct gene-loaded IMANS, but we did not reassess the immunoreactivity of gene-loaded IMANS.…”