期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.2c00794
关键词
graphene quantum dots; metal doping; ultrasound contrast agent; visible fluorescence; near-infrared fluorescence; ultrasound imaging; confocal imaging
Sonography offers advantages of non-invasiveness, deep tissue penetration, and low cost. The combination of ultrasound contrast agents with visible and NIR fluorophores can overcome the lack of high precision imaging. Metal-doped NGQDs demonstrate high-contrast ultrasound brightness mode properties and visible/NIR fluorescence imaging capabilities. They have potential for various theragnostic applications.
Sonography offers many advantages over standard methods of diagnostic imaging due to its non-invasiveness, substantial tissue penetration depth, and low cost. The benefits of ultrasound imaging call for the development of ultrasound-trackable drug delivery vehicles that can address a variety of therapeutic targets. One disadvantage of the technique is the lack of high precision imaging, which can be circumvented by complementing ultrasound contrast agents with visible and, especially, near-infrared (NIR) fluorophores. In this work, we, for the first time, develop a variety of lightly metal-doped (iron oxide, silver, thulium, neodymium, cerium oxide, cerium chloride, and molybdenum disulfide) nitrogen-containing graphene quantum dots (NGQDs) that demonstrate high-contrast properties in the ultrasound brightness mode and exhibit visible and/or near-infrared fluorescence imaging capabilities. NGQDs synthesized from glucosamine precursors with only a few percent metal doping do not introduce additional toxicity in vitro, yielding over 80% cell viability up to 2 mg/mL doses. Their small (<50 nm) sizes warrant effective cell internalization, while oxygen-containing surface functional groups decorating their surfaces render NGQDs water soluble and allow for the attachment of therapeutics and targeting agents. Utilizing visible and/or NIR fluorescence, we demonstrate that metal-doped NGQDs experience maximum accumulation within the HEK293 cells 6-12 h after treatment. The successful 10-fold ultrasound signal enhancement is observed at 0.5-1.6 mg/mL for most metal-doped NGQDs in the vascular phantom, agarose gel, and animal tissue. A combination of non-invasive ultrasound imaging with capabilities of high-precision fluorescence tracking makes these metal-doped NGQDs a viable agent for a variety of theragnostic applications.
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