S-Y Lee, M-J Shieh
National Taiwan University,
Keywords: gold nanoshells, micelles, chemotherapy, photothermal therapy
Summary:Gold nanoshells have attracted great research interest because of its potential application in cancer photothermal therapy. In the present study, we established a multifunctional gold nanoshell that directly utilizing positively charged PDMA-b-PCL micelles as a template. The PDMA- b-PCL micelles with positive surface charge (32 ~ 35 mV) can attract negatively charged AuCl4-, and then AuCl4- was reduced by the reducing agent and forming a gold layer on the micellar surface. The average hydrodynamic diameter of PDMA-b-PCL micelles was 93.4±0.96 nm. The size of synthesized gold nanoshells (GNS) increased to 167.1±2.40 nm due to the successful coating of gold shell. The SN-38-encapsulated micelles (SN-38@M) were 121.3±1.46 nm in diameter. After coating with gold shells, the SN-38-loaded GNS (SN-38@GNS) were 131.1±1.60 nm in diameter. The drug encapsulation efficiency of SN-38@M was 46.7±9.16%, and that of SN-38@GNS was 81.2±1.90%. TEM images of SN-38@M and SN-38@GNS showed the synthized GNS were spherical and uniform in size. The empty GNS and SN-38@GNS were then functionalized with thio-PEG in order to improve their biocompatibility and prolong the in vivo circulation time for future applications. The absorbance spectra of pGNS and SN-38@pGNS both revealed a broad absorption band between 500 and 1000 nm. The strong absorption in the near-infrared (NIR) region allows GNS to be a potential photothermal mediator for cancer therapy. To investigate the photothermal characteristics of GNS, the temperature changes of GNS solutions were measured under the NIR laser irradiation. Both pGNS and SN-38@pGNS exhibited excellent photothermal conversion ability, with a temperature increase of 60°C within 2 min of irradiation. Then we used MTT assay to study the therapeutic effect of the synthesised multifunctional GNS in a human colon cancer cell line, HCT116. The NIR irradiation itself did not significantly decreased the cell viability, indicating the irradiation condition is safe for HCT116. The pGNS-treated group had more than 70% of cells remained viable, suggesting an acceptable level of biocompatibility of the empty pGNS. The combined therapy involving SN-38@pGNS and NIR laser irradiation resulted in a significant anticancer effect, while the photothermal therapy (pGNS plus laser irradiation) only showed limited therapeutic effect. In summary, we established a multifunctional gold nanoshell (GNS) by utilizing positively charged PDMA-b-PCL micelles as the template. The GNS with micellar core enable the delivery of the hydrophobic chemotherapeutic, SN-38. The synthesized SN-38@pGNS had a spherical morphology and a narrow size distribution. With the exposure to NIR laser irradiation, SN-38@pGNS exhibited an excellent photothermal conversion efficiency. As shown in the result of in vitro study, The combination of chemotherapy and photothermal therapy resulted in a significant anticancer effect. These results suggested the gold nanoshells with micellar core can serve not only as a photothermal mediator but also a delivery system for hydrophobic drugs. Therefore, the gold nanoshells with PDMA-b-PCL micellar core we reported here could be applied as a potential multifunctional therapeutics for cancer therapy in the future.