Nanostructured Medicine Vector For Gene/Drug Co-delivery

Although considerable progresses have been made in the study on the delivery of gene and drugs, many kind of nanoparticles with different chemical nature and surface topography are still developing. Literature presented in this review clearly indicates that nanoparticles can efficiently induce endocytosis and deliver gene and drugs into cancer cells. Many of the studies are still qualitative and produce different coatings with a similar platform. Variations in nanosized core, coatings and cell types would introduce variability in the experimental results. In clinical gene therapy by nanoparticles, higher transfection efficiency is still needed, as well as biocompatibility, long-term biodegradation,and site-selective application. In summary, nanoparticles offer many ways for preparation with a defined particle size, surface functionalization, biocompatibility, and nucleic acid protection. And more efficient carriers would be designed in future.1. Bifunctional pH-Sensitive Zn(Ⅱ)-Curcumin Nanoparticles/siRNA Effectively Inhibit Growth of Human Bladder Cancer Cells in Vitro and in VivoTo overcome drug resistance, the combination of two or more therapeutic strategies with different mechanisms has been received much attention in recent years. In this study, a common approach has been used to process curcumin and Zn2+into colloidal dispersions known as "nanoparticles", which is cheap and simple to prepare with high reproducibility. This novel vehicle has good biocompatibility and high cellular uptake for simultaneously delivering curcumin drug and siRNA into tumor cells. Complexation of Zn2+with curcumin enhances the aqueous solubility of hydrophobic drug curcumin and further improves the cellular uptake and bioavailability. The acid-labile coordination Zn(Ⅱ)-O bond in Zn(Ⅱ)-curcumin drug nanoparticles (Zn(Ⅱ)-Cur NPs) can respond to tumor intracellular acidic pH environments to release curcumin, and promoting acid-triggered intracellular drug release. The positively charged Zn(Ⅱ)-Cur NPs can efficiently deliver siRNA into human bladder cancer cells, protect siRNA against enzymatic degradation, and facilitate the escape of loaded siRNA from the endosome into the cytoplasm, which successfully downregulates the targeted EIF5A2oncogene and consequently inhibits cancer cell growth in vitro and in vivo. Proliferation and migration of cancer cells are inhibited by silencing the expression of EIF5A2and increasing the ratio of pro-apoptotic BAX to anti-apoptotic BCL-2. In vitro and in vivo experiments have demonstrated that bifunctional Zn(II)-Cur NPs/siEIF5A2can combine chemotherapy with gene therapy to afford higher therapeutic efficacy than the individual therapeutic protocols2. Synergistic Anticancer Activity of Fe(II)-Catechin and siRNA for Human Bladder Cancer Cells in Vitro and in VivoCancer is the first leading cause of death in the China and in many other nations in the world. The bladder cancer represents the ninth most common malignancy worldwide. Green tea is now confirmed to be the most effective food for cancer prevention. The green tea catechin has been studied for cancer preventive activity. As a naturally produced compound from common beverage, catechin induces much less side effects than other medicine used for chemical therapy. Herein, we use catechin natural drug itself to directly fabricate a nanocarrier with Fe2+ions. The ability to induce apoptosis in bladder cancer cell using the T24cell line is investigated both in vitro and in vivo. The obtained Fe(Ⅱ)-Cat/siEIF5A2have shown high transfection efficiency and few side effects based on the synergistic use of chemotherapy and gene therapy methods. In vivo experiments show that Fe (Ⅱ)-Cat/siEIF5A2and Fe (Ⅱ)-Cat can effectively control the morphology of the tumor and inhibit the proliferation of tumor progression.3. Graphene wrapped magnetic nanoparticles:Dipole-directed assembly of Fe3O4nanoparticles into nanorings via oriented attachmentWe have developed a novel hydrothermal method to fabricate Fe3O4ring-like nanostructures via oriented attachment of Fe3O4nanoparticles through intermediate Fe3O4platelets. The obtained samples were characterized by X-ray diffraction (XRD) analysis, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selective-area electron diffractometry (SAED), high-resolution TEM (HRTEM) and vibrating-sample magnetometer (VSM). A reasonable mechanism based on the self-assembly of magnetic Fe3O4nanoparticles on graphene nanosheets using inorganic ions as crystal growth modifiers is proposed. The intrinsic dipole-dipole interactions between the individual magnetic Fe3O4nanoparticles act as the driving force for nanoring formation. Saturation moment of the superparamagnetic Fe3O4nanorings is much higher than that of the corresponding unassembled nanoparticles. The enhancement of saturation moment is due to the oriented ring-like assembly with synergistic magnetism. This study could provide an additional tool for fabricating other nanostructures via oriented attachment...