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The therapeutic efficacy of systemic drug delivery vehicles depends on their ability to evade the immune system, cross the biological barriers of the body and localize at target tissues. Leukocytes possess all of these functions and exert their targeting ability through cellular membrane interactions. Here we show that NanoPorous Silicon particles (NPS) can successfully perform all these actions when coated with cellular membranes purified from white blood cells. These hybrid particles called LeukoLike Vectors (LLV) were able to: prevent rapid clearance of phagocytic cells of the immune system; communicate with endothelial cells through receptor-ligand interaction; transport and release a payload across an inflamed reconstructed endothelium. Furthermore, LLV retained their functions when injected in vivo, showing enhanced circulation time and improved accumulation in the tumour.
Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.