title: Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems.
abstract: New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.
authors.affiliation: Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghasemi
authors.affiliation: Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran.
authors.forename: Parham
authors.initials: P
authors.lastname: Sahandi Zangabad
authors.affiliation: Department of Research and Development, Sharif Ultrahigh Nanotechnologists (SUN) Company, P.O. Box: 13488-96394, Tehran, Iran and Nanotechnology Research Center, Research Institute of Petroleum Industry (RIPI), West Entrance Blvd., Olympic Village, P.O. Box: 14857-33111, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahighi
authors.affiliation: Bioenvironmental Research Center, Sharif University of Technology, Tehran, Iran and Civil & Environmental Engineering Department, Shahid Beheshti University, Tehran, Iran.
authors.forename: S Masoud
authors.initials: SM
authors.lastname: Moosavi Basri
authors.affiliation: Department of Biotechnology, University of Kerala, Trivandrum, India.
authors.forename: H
authors.initials: H
authors.lastname: Mirshekari
authors.affiliation: Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Amiri
authors.affiliation: Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Z
authors.initials: Z
authors.lastname: Shafaei Pishabad
authors.affiliation: Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Aslani
authors.affiliation: Department of Applied Chemistry, Central Branch of Islamic Azad University of Tehran, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Bozorgomid
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: D
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: School of Mechanical Engineering, Boston University, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Beyzavi
authors.affiliation: Department of Biotechnology, Faculty of Advanced Science and Technologies of Isfahan, Isfahan, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Vaseghi
authors.affiliation: Department of Cancer Biology, Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Department of Genetics, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Aref
authors.affiliation: School of Medicine, International Campus of Tehran University of Medical Science, Tehran, Iran.
authors.forename: L
authors.initials: L
authors.lastname: Haghani
authors.affiliation: Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Bahrami
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Hamblin@helix.mgh.harvard.edu and Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA and Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D004364:Pharmaceutical Preparations; D004247:DNA