In this work, protein-modified hydrophilic copper sufide (CuS) nanotriangles with tunable absorption in the second near-infrared (NIR-II) region are developed, which can be served as contrast agents for enhanced in vivo photoacoustic imaging. In vitro and in vivo toxicity analysis are also performed, which show that the nanoprobes are biocompatible for most of the test cases. As a result, the nanoprones is able to pave a new avenue for improving the photoacoustic imaigng contrast and penetration depth in cancer detection. It should be pointed out that other functional blocks may also be linked on it, which makes it a general method to design multifunctional nanoprobes.