Gas-loaded PLA Nanoparticles as Ultrasound Contrast Agents

Abstract

Poly (D,L-lactic acid) is being investigated as a platform material for nano-sized ultrasound contrast agents. To overcome the weak echogenicity encountered with these particles, gas-filled nanoparticles have been designed. Sublimable porogens such as camphor were added to render the nanoparticles hollow and enable efficient gas introduction. Sulfur hexafluoride gas (SF₆), a hydrophobic and dense bioinert gas, was introduced to enhance backscattered signals. Factors that may affect the physical and acoustic properties of particles were considered to optimize a gas-filled nanoparticles preparation method. Dynamic light scattering and atomic force microscopy results demonstrated that the nanoparticles have approximately 200 nm in size with a unimodal distribution and spherical shape. This result suggests that the particles could be accumulated at solid tumor sites passively via well known EPR (Enhanced Permeability and Retention) effect. Acoustic enhancement by particles containing SF₆ gas at 5 MHz frequency was superior to those containing air. The crucial role of hydrophobic porogen, camphor, on improving echogenicity of nanoparticles has been confirmed with further experiments. In conclusion, this study presents pioneering work to develop ultrasound imaging using nanobiotechnolgy.