Nanobubble-embedded inorganic 808 nm excited upconversion nanocomposites for tumor multiple imaging and treatment

Abstract

Contrast reagents for ultrasound imaging are widely used in clinical medical diagnosis because ultrasound resolution is limited. Contrast agents must be utilized to enhance the image resolution. At present, microbubbles (MBs) and nanobubbles (NBs) are the main contrast reagent candidates for improving the signal resolution. Fluorescence upconversion nanoparticles provide high sensitivity and also function as nanocarriers. This can label tumor cells in a specific organ under irradiation of near-infrared (NIR) light. However, despite the use of NIR light, the penetration depth of NIR is only approximately 15 mm. Thus, we combine fluorescence with ultrasonic imaging to achieve the effect of multiple imaging and solve the low penetration depth of fluorescence imaging and the poor resolution of ultrasound imaging. The dual imaging modalities achieved higher resolution or signal to noise ratios. In this study, Nd³⁺-sensitized upconversion nanoparticles (UCNPs) are combined with graphitic carbon nitride quantum dots (CNs) and embedded in NBs (UCNP–CN@NBs). The UCNPs are excited by 808 nm light and emit visible and ultraviolet light. Then, the energy of the ultraviolet light is transferred to the CNs to produce reactive oxygen species (ROS) for photodynamic therapy. Ultrasonic waves are also used to promote NB bursting and the release of ROS molecules in photodynamic therapy, leading to cancer cell apoptosis.