The therapeutic efficacy of systemic drug delivery vehicles depends on their ability to evade the immune system, cross biological barriers, and localize at target tissues. Leukocytes possess these functions and exert their targeting ability through cellular membrane interactions. This study demonstrates that NanoPorous Silicon (NPS) particles can successfully perform these actions when coated with cellular membranes purified from white blood cells, resulting in hybrid particles called LeukoLike Vectors (LLV). LLV were able to prevent rapid clearance by phagocytic cells, communicate with endothelial cells through receptor-ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. In vivo experiments showed that LLV retained their functions, exhibiting enhanced circulation time and improved accumulation in tumors. The biomimetic camouflage strategy provided a competitive advantage for overcoming sequential vascular barriers by reducing opsonization, leveraging self-recognition mechanisms to delay phagocytic uptake, binding to inflamed endothelium, and facilitating transport across the endothelial layer while avoiding lysosomal pathway. These findings suggest that LLV may be well-suited for chemotherapeutic delivery to cancer.The therapeutic efficacy of systemic drug delivery vehicles depends on their ability to evade the immune system, cross biological barriers, and localize at target tissues. Leukocytes possess these functions and exert their targeting ability through cellular membrane interactions. This study demonstrates that NanoPorous Silicon (NPS) particles can successfully perform these actions when coated with cellular membranes purified from white blood cells, resulting in hybrid particles called LeukoLike Vectors (LLV). LLV were able to prevent rapid clearance by phagocytic cells, communicate with endothelial cells through receptor-ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. In vivo experiments showed that LLV retained their functions, exhibiting enhanced circulation time and improved accumulation in tumors. The biomimetic camouflage strategy provided a competitive advantage for overcoming sequential vascular barriers by reducing opsonization, leveraging self-recognition mechanisms to delay phagocytic uptake, binding to inflamed endothelium, and facilitating transport across the endothelial layer while avoiding lysosomal pathway. These findings suggest that LLV may be well-suited for chemotherapeutic delivery to cancer.