A new combination cancer treatment has emerged and is seeing remarkable results in the fight against cancer. In a new study, a team of scientists prepared a theranostic nanoformulation that allows for photoacoustic imaging as well as combination gene and photothermal therapy. Gold nanorods (GNR) were coated with dipicolylamine (DPA), which forms stable complexes with Zn2+ cations. The resulting nanoparticles, Zn(II)/DPA-GNR, recognize phosphate-containing molecules, including siRNA, because of the specific interaction between Zn(II) and the phosphates. The team chose anti-polo-like kinase 1 siRNA (siPLK) as the example for their gene silencing treatment. The strong complexation between Zn(II)/DPA-GNR and siPLK provided high stability to the nano-complexes, which efficiently delivered siRNA into the targeted cancer cells in vitro and in vivo. The particle served as a theranostic agent because the GNRs of nano-complexes permitted effective photothermal therapy as well as photoacoustic imaging upon laser irradiation. This gene/photothermal combination therapy using siPLK/Zn(II)DPA-GNRs exhibited significant antitumor activity in a PC-3 tumor mouse model. The research described in this study may be extended to the development of efficient delivery strategies for other polynucleotides as well as advanced anticancer therapy.
Measurement of Photothermal Effect of ZD-GNRs
ZD-GNRs were diluted into different concentrations with distilled water. Aliquots of samples were exposed to an 808 nm NIR laser (Laserglow Technologies) for 10 min at varying intensity levels. A laser energy meter was used to measure and calibrate the laser densities. The temperature increase of the solutions was recorded with an infrared thermal imaging system.
The team next investigated the photothermal effect of the ZD-GNRs. Because the gold nanorods have peak absorbance around 800 nm, 808 nm laser source is suitable for photothermal experiments. Different concentrations of ZD-GNRs were evaluated at a fixed intensity (1.0 W/cm2) for 10 min. The temperature change of GD-GNRs in the cell culture medium was monitored upon laser irradiation. The cell culture without particles showed almost no heating effect. However, the Zn-GNR treatment followed by 1.0 W/cm2 laser treatment raised the median temperature by about 30 °C within 10 min which is high enough for cell killing. Taken together, the results above confirmed that the siRNA/ZD-GNRs can effectively deliver siRNA into cells, silence target genes, and have a photothermal effect by gold nanorods upon laser irradiation.
The team successfully developed siRNA-complexed Zn(II)-DPA conjugated gold nanorods (siRNA/ZD-GNRs) through an artificial siRNA receptor, Zn(II)-DPA, which can strongly bind siRNA molecules for combined gene and photothermal tumor treatment. The introduction of gold nanorods with Zn(II)-DPA as a siRNA delivery carrier provided not only sufficient complexation with siRNA in the form of stable nanoparticles, which show strong gene-silencing activity, but also photothermal property of GNRs upon laser irradiation. Moreover, the application of siPLK/ZD-GNRs for gene/photothermal combination therapy demonstrates synergistic antitumor efficacy, which is significantly better than individual gene therapy or PTT alone. Additionally, due to the photoacoustic character of GNRs, siRNA/ZD-GNRs have great potential as a theranostic agent for simultaneous PA imaging and therapy of cancers. The approach suggested in this work may provide a valuable general strategy for efficient combination treatment of cancer.
Full access to the materials and methodology, can be found by clicking here.
Details on the 808 nm NIR Laser used in the research can be found by clicking here.