Abstract
The current positive computed tomography (CT) contrast agents (PCTCAs) including clinical iodides, present high CT density value (CT-DV). However, they are incapable for the accurate diagnosis of some diseases with high CT-DV, such as osteosarcoma. Because bones and PCTCAs around osteosarcoma generate similar X-ray attenuations. Here, an innovative strategy of negative CT contrast agents (NCTCAs) to reduce the CT-DV of osteosarcoma is proposed, contributing to accurate detection of osteosarcoma. Hollow mesoporous silica nanoparticles, loading ammonia borane molecules and further modified by polyethylene glycol, are synthesized as NCTCAs for the diagnosis of osteosarcoma. The nanocomposites can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, resulting in nearly 20 times reduction of CT density in osteosarcoma. This helps form large CT density contrast between bones and osteosarcoma, and successfully achieves accurate diagnosis of osteosarcoma. Meanwhile, The NCTCAs strategy greatly expands the scope of CT application, and provides profound implications for the precise clinical diagnosis, treatment, and prognosis of diseases.