title: Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer?
abstract: Nanotechnology offers several attractive design features that have prompted its exploration for cancer diagnosis and treatment. Nanosized drugs have a large loading capacity, the ability to protect the payload from degradation, a large surface on which to conjugate targeting ligands, and controlled or sustained release. Nanosized drugs also leak preferentially into tumor tissue through permeable tumor vessels and are then retained in the tumor bed due to reduced lymphatic drainage. This process is known as the enhanced permeability and retention (EPR) effect. However, while the EPR effect is widely held to improve delivery of nanodrugs to tumors, it in fact offers less than a 2-fold increase in nanodrug delivery compared with critical normal organs, resulting in drug concentrations that are not sufficient for curing most cancers. In this Review, we first overview various barriers for nanosized drug delivery with an emphasis on the capillary wall's resistance, the main obstacle to delivering drugs. Then, we discuss current regulatory issues facing nanomedicine. Finally, we discuss how to make the delivery of nanosized drugs to tumors more effective by building on the EPR effect.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892-1088, United States.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892-1088, United States.
authors.forename: Ai
authors.initials: A
authors.lastname: Mochida
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892-1088, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892-1088, United States.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002199:Capillary Permeability; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D050997:Nanomedicine / Q000331:legislation & jurisprudence / Q000379:methods; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D016499:Radioimmunotherapy / Q000379:methods; D014481:United States; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D014665:Vasodilator Agents