Microbubbles based contrast-enhanced ultrasound plays a more and more important role in oncology1. However, the utility of ultrasound for molecular imaging is significantly limited due to the lack of nanoscale contrast agents that can penetrate through tumor vasculature via the Enhanced Permeability and Retention (EPR)effect2. Recently reported gas vesicles (GVs), isolated from buoyant photosynthetic microbes, demonstrated significant potentials as a novel nanoscale contrast agent for ultrasound molecular imaging3-4. However, the actual capability of GVs to penetrate through EPR and reach tumor site has not been demonstrated. In this research, we evaluated the bio-distribution of GVs in subcutaneous mouse tumor model with in vivo fluorescence imaging and ultrasound imaging, respectively, and studied the GV s biosafety by tissue toxicity assessment.