Treatment of three-dimensional (3D) tumor spheroids with C34 and the analysis of annexin V/propidium iodide (PI) staining after US irradiation showed that the proportion of apoptotic and/or necrotic cells increased from the edge to the core of tumor spheroids as time increased (Fig. 3D), suggesting the good multilayer cellular penetrability of C34. Here, ANXA5 is linked to neoplasm.