title: Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology.
abstract: Cancer nanotherapeutics are progressing at a steady rate; research and development in the field has experienced an exponential growth since early 2000's. The path to the commercialization of oncology drugs is long and carries significant risk; however, there is considerable excitement that nanoparticle technologies may contribute to the success of cancer drug development. The pace at which pharmaceutical companies have formed partnerships to use proprietary nanoparticle technologies has considerably accelerated. It is now recognized that by enhancing the efficacy and/or tolerability of new drug candidates, nanotechnology can meaningfully contribute to create differentiated products and improve clinical outcome. This review describes the lessons learned since the commercialization of the first-generation nanomedicines including DOXIL® and Abraxane®. It explores our current understanding of targeted and non-targeted nanoparticles that are under various stages of development, including BIND-014 and MM-398. It highlights the opportunities and challenges faced by nanomedicines in contemporary oncology, where personalized medicine is increasingly the mainstay of cancer therapy. We revisit the fundamental concepts of enhanced permeability and retention effect (EPR) and explore the mechanisms proposed to enhance preferential "retention" in the tumor, whether using active targeting of nanoparticles, binding of drugs to their tumoral targets or the presence of tumor associated macrophages. The overall objective of this review is to enhance our understanding in the design and development of therapeutic nanoparticles for treatment of cancers.
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertrand
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Nazila
authors.initials: N
authors.lastname: Kamaly
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA. Electronic address: ofarokhzad@zeus.bwh.harvard.edu.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents
keywords: Active targeting; Drug delivery; Enhanced permeation and retention effect; Imaging; Nanomedicine; Nanoparticles; Patient enrichment; Personalized medicine; Tumor microenvironment; Vessel normalization