title: Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target?
abstract: Nano-sized therapeutic agents have several advantages over low molecular weight agents such as a larger loading capacity, the ability to protect the payload until delivery, more specific targeting due to multivalency and the opportunity for controlled/sustained release. However, the delivery of nano-sized agents into cancer tissue is problematic because it mostly relies on the enhanced permeability and retention (EPR) effect that depends on the leaky nature of the tumor vasculature and the prolonged circulation of nano-sized agents, allowing slow but uneven accumulation in the tumor bed. Delivery of nano-sized agents is dependent on several factors that influence the EPR effect; 1. Regional blood flow to the tumor, 2. Permeability of the tumor vasculature, 3. Structural barriers imposed by perivascular tumor cells and extracellular matrix, 4. Intratumoral pressure. In this review, these factors will be described and methods to enhance nano-agent delivery will be reviewed.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Rira
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002199:Capillary Permeability; D006801:Humans; D049329:Nanostructures / Q000627:therapeutic use; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; Enhanced permeability and retention effects.; Nano-delivery; Tumor physiology