Cancer Screening by Systemic Administration of a Gene Delivery Vector Encoding Tumor-Selective Secretable Biomarker Expression

Cancer biomarkers facilitate screening and early detection but are known for only a few cancer types. We demonstrated the principle of inducing tumors to secrete a serum biomarker using a systemically administered gene delivery vector that targets tumors for selective expression of an engineered cassette. We exploited tumor-selective replication of a conditionally replicative Herpes simplex virus (HSV) combined with a replication-dependent late viral promoter to achieve tumor-selective biomarker expression as an example gene delivery vector. Virus replication, cytotoxicity and biomarker production were low in quiescent normal human foreskin keratinocytes and high in cancer cells in vitro. Following intravenous injection of virus >90% of tumor-bearing mice exhibited higher levels of biomarker than non-tumor-bearing mice and upon necropsy, we detected virus exclusively in tumors. Our strategy of forcing tumors to secrete a serum biomarker could be useful for cancer screening in high-risk patients, and possibly for monitoring response to therapy. In addition, because oncolytic vectors for tumor specific gene delivery are cytotoxic, they may supplement our screening strategy as a “theragnostic” agent. The cancer screening approach presented in this work introduces a paradigm shift in the utility of gene delivery which we foresee being improved by alternative vectors targeting gene delivery and expression to tumors. Refining this approach will usher a new era for clinical cancer screening that may be implemented in the developed and undeveloped world

Magnetic Iron Oxide Nanoparticles: Synthesis and Surface Functionalization Strategies

Surface functionalized magnetic iron oxide nanoparticles (NPs) are a kind of novel functional materials, which have been widely used in the biotechnology and catalysis. This review focuses on the recent development and various strategies in preparation, structure, and magnetic properties of naked and surface functionalized iron oxide NPs and their corresponding application briefly. In order to implement the practical application, the particles must have combined properties of high magnetic saturation, stability, biocompatibility, and interactive functions at the surface. Moreover, the surface of iron oxide NPs could be modified by organic materials or inorganic materials, such as polymers, biomolecules, silica, metals, etc. The problems and major challenges, along with the directions for the synthesis and surface functionalization of iron oxide NPs, are considered. Finally, some future trends and prospective in these research areas are also discussed

Surface modification of permalloy (Ni80Fe20) nanoparticles for biomedical applications

We report a simple and novel method for surface biofunctionalization onto recently reported NiFe permalloy nanoparticles (~71 nm) and the immobilization of a model protein, IgG from human serum. The strategy of protein immobilization involved attachment of histidine-tagged streptavidin to the NiFe nanoparticles via a non-covalent ligand binding followed by biotinylated human IgG binding on the nanoparticle surface using the specific high affinity avidin-biotin interaction. The biofunctionalization of NiFe permalloy nanoparticles was confirmed by Fourier Transform InfraRed (FTIR) spectroscopy and protein denaturing gel electrophoresis (lithium dodecyl sulfate- polyacrylamide gel electrophoresis, LDS-PAGE). This protocol for surface functionalization of the novel nanometer-sized NiFe permalloy particles with biological molecules could open diverse applications in disease diagnostics and drug delivery