Laser-Activatible Gold Particles for Phase Transformation Imaging and Therapy in Metastatic Lymph Nodes

Abstract

The gold nanoparticles were incorporated into PLGA/PFH (Au-PLGA/PFH) particles to observe their enhanced ultrasound imaging and treatment effect in rabbit metastatic lymph nodes. Double emulsion evaporation method was used to prepare the Au-PLGA/PFH particles. The size distribution, the morphological and structural characterization, the optical obsorbing property were estimated. The rabbit VX2 tumor was inoculated in rabbits subcutaneous thigh muscles to build popliteal lymph node metastasis of tumor models. After the Au-PLGA/PFH particles were introduced into lymph nodes by rabbit footpad, US were used to image the popliteal lymph nodes in real-time, also the Color Doppler Flow Image (CDFI) were acquired. With a wavelength of 532nm laser irradiation in vitro, the image of lymph nodes were observed under 2D and contrast enhance mode. Improving the laser energy, the irradiation was done every 48 h for a total of three times, this process was observed by US and CDFI. 48 h after the last irradiation, the rabbits were sacrificed, and the lymph node tissue were removed to measure the size, also the HE, immunohistochemistry and transmission electron microscopy (TEM) measurement were carried. The Au-PLGA/PFH particle is about 1 μm in diameter, the gold nanoparticles are located around the shell, these are clearly visible as small black dots in the PLGA shell. A UV-Vis shows there is a strong optical obsorbing peak of the particles in 525nm. Thus, with a 532 nm laser irradiation in vitro, the particles in lymph nodes absorb light energy to enhance the local temperature, when the temperature is over the phase transition threshold of PFH, the particles transfer into bubbles and enhance the US imaging. In addition, as the laser fluence increased, the creating bubble that expanded within the tumor cells, eventually destroyed the cells. Therefore, the lymph nodes enlarge slowly or smaller than before. HE, immunohistochemisty and TEM further conform this effect. This work demonstrates PLGA/PFH particles containing gold nanoparticles can use as US contrast agents and theragnostic agents.