Application Of Gold Nanoparticles In Tumor Imaging And Treatment

Gastric cancer?GC?is a cancer that arises from the lining of the stomach.More than 95%of this heterogeneous disease is adenocarcinoma that can be subdivided into two main hisological subtypes:intestinal and diffuse.Gastric cancer is the third most common cause of cancer-related death in the world,and it remains difficult to cure.With the rapid development of nanotechnology and its applications,a wide variety of engineered nanostructure materials are now used in pharmaceuticals,biomedical products and other industries.Gold nanopaticles are widely used in many fileds as preferred materials for their unique optical and physical properties.In our study,a novel nano-platform?GNS@CaCO₃/ICG?consisting of calciumcarbonate-encapsulated gold nanostars loaded with ICG was established to couple the photothermal properties of gold nanostars?GNSs?and the photodynamic properties of indocyanine green?ICG?in the photodynamic/photothermal combination therapy?PDT/PTT?.The calcium carbonate worked not only a drug keeper to entrap ICG on the surface of GNSs in the form of a stable aggregate which was protected from blood clearance,but also as the a pH-responder to achieve highly effective tumor-triggered drug release locally.The application of GNS@CaCO₃/ICG for in vitro and in vivo therapy achieved the combined antitumor effects upon the NIR irradiation,which was superior to the single PDT or PTT.Meanwhile,the distinct pH-triggered drug release performance of GNS@CaCO₃/ICG implemented the tumor-targeted NIR fluorescence imaging.In addition,we monitored the bio-distribution and excretion pathway of GNS@CaCO₃/ICG based on the NIR fluorescence from ICG and two-photon fluorescence and photoacoustic signal from GNSs,and the results proved that GNS@CaCO₃/ICG had a great ability for tumor-specific and tumor-triggered drug release.Next,we prepared a novel nanoplatform?AuNRs-iPS?with photothermal therapeutic effects by fabricating AuNRs@SiO₂@CXCR4 nanoparticles and loading the prepared nanoparticles into the human induced pluripotent stem?iPS?cells.In virtue of the prominent optical properties of AuNRs@SiO₂@CXCR4 and remarkable tumor target migration ability of iPS cells,the AuNRs delivery mediated by iPS cells via the nanoplatform AuNRs-iPS was found to have a prolonged retention time and spatially even distribution in MGC803 tumor-bearing nude mice observed by photoacoustic tomography and two-photon luminescence.Based on these improvements,the nanoplatform displayed a robust migration capacity to target the tumor site and to improve photothermal therapeutic efficacy on inhibiting the growth of tumors in xenograft mice under a low laser power density.Finally,we selected four kinds of common metal nanoparticles such as magnetic nanoparticles,silver triangle nanoparticles,gold nanoclusters and gold nanorods as traker.These metal nanoparticles were prepared and characterized,and injected via tail vein into a mice model with common bile duct?CBD?ligation.The feces and urines were collected for seven days to be followed by the sacrifice of the mice and collection of the intestinal and gastric tissues for further analysis.The results showed that all four selected metal nanoparticles were located inside the goblet cells?GCs?of the whole intestinal tissue and were excreted into the gut lumen through the secretion of intestinal GC.Moreover,triangular silver nanoplates and gold nanorods were located inside the gastric parietal cells?PCs?.Importantly,nanoparticles did not cause pathological changes of intestinal tissues.In this study,we confirmed that the blood corpuscles are involved in the GCs secretion pathway.Furthermore,we found that the secretion of nanoparticles from intestinal GCs and PCs is accelerated by diarrhea.In conclusion,metal nanoparticles such as triangular silver nanoplates,magnetic nanoparticles,gold nanorods and gold nanoclusters can be cleaned away by intestinal GCs and PCs.